Research Overview

Timothy A. Springer discovered with monoclonal antibodies, then cloned and functionally and structurally characterized, many of the adhesion receptors in the immune system. He was the first to demonstrate that lymphocytes and leukocytes had adhesion molecules. His work on these receptors has advanced to characterizing their interactions and allosteric transitions by x-ray crystallography, electron microscopy, and laser tweezers force spectroscopy. His discoveries directly led to the development and FDA approval of Efalizumab, an antibody to LFA-1, and Alefacept, an LFA-3 Fc fusion, both for plaque psoriasis.

Dr. Springer later discovered the three-step paradigm for leukocyte diapedesis: 1) rolling adhesion of leukocytes on the vessel wall through selectins; 2) activation of G protein-coupled receptors on the leukocyte by chemoattractants; and 3) activation of integrin adhesiveness for CAMs on endothelium, which mediates firm adhesion and diapedesis. These discoveries led him to found LeukoSite in 1993. LeukoSite developed three FDA approved therapeutics, including vedolizumab (Entyvio), an antibody to integrin alpha4 beta7 approved for moderate to severe ulcerative colitis and Crohn's disease in 2014. LeukoSite was acquired in 1999 by Millennium Pharmaceuticals.

Dr. Springer’s academic interests now focus on how protein conformational change together with tensile force activates integrins, von Willebrand factor, the transforming growth factor-beta family, and adhesins on malaria sporozoites, and discovering new binding partners. Currently, he is a successful private investor in biotech with seats on five corporate and two non-profit boards. His newest endeavor is the Institute for Protein Innovation, a non-profit to advance entrepreneurship and innovation in protein therapeutics and open-source antibodies and small molecules.

Research Background

Timothy A. Springer is Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and the Program of Cellular and Molecular Medicine at Boston Children’s Hospital. Dr. Springer graduated from the University of California, Berkeley, and earned a Ph.D. in molecular biology and biochemistry from Harvard University. He is a member of the National Academy of Sciences and the American Academy of Arts and Sciences. In 2004, he was co-recipient of the prestigious Crafoord Prize given by the Royal Swedish Academy of Sciences. Dr. Springer is the recipient of the 2019 Canada Gairdner International Award, recognizing his “seminal discoveries and major scientific contributions constitut[ing] an original and significant achievement in biomedical science.”

Dr. Springer was the 2022 recipient of the Lasker Basic Medical Research Award and was elected to the National Academy of Medicine in 2023.

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On Answers

Tim Springer, PhD, winner of the 2022 Lasker Basic Medical Research Award

Publications

  1. De Novo Design of Integrin a5ß1 Modulating Proteins for Regenerative Medicine. bioRxiv. 2024 Jul 10. View Abstract
  2. Synthetic integrin antibodies discovered by yeast display reveal aV subunit pairing preferences with ß subunits. MAbs. 2024 Jan-Dec; 16(1):2365891. View Abstract
  3. Ligand binding initiates single-molecule integrin conformational activation. Cell. 2024 Jun 06; 187(12):2990-3005.e17. View Abstract
  4. Synthetic integrin antibodies discovered by yeast display reveal aV subunit pairing preferences with ß subunits. bioRxiv. 2024 Jan 27. View Abstract
  5. De novo design of highly selective miniprotein inhibitors of integrins avß6 and avß8. Nat Commun. 2023 09 13; 14(1):5660. View Abstract
  6. Structural insights into MIC2 recognition by MIC2-associated protein in Toxoplasma gondii. Commun Biol. 2023 08 31; 6(1):895. View Abstract
  7. De novo design of highly selective miniprotein inhibitors of integrins avß6 and avß8. bioRxiv. 2023 Jun 12. View Abstract
  8. Conformational change of Plasmodium TRAP is essential for sporozoite migration and transmission. EMBO Rep. 2023 Jul 05; 24(7):e57064. View Abstract
  9. A recombinant technique for mapping functional sites of heterotrimeric collagen helices: Collagen IV CB3 fragment as a prototype for integrin binding. J Biol Chem. 2023 07; 299(7):104901. View Abstract
  10. A specialized integrin-binding motif enables proTGF-ß2 activation by integrin aVß6 but not aVß8. Proc Natl Acad Sci U S A. 2023 06 13; 120(24):e2304874120. View Abstract
  11. Conformation of von Willebrand factor in shear flow revealed with stroboscopic single-molecule imaging. Blood. 2022 12 08; 140(23):2490-2499. View Abstract
  12. Single-molecule characterization of subtype-specific ß1 integrin mechanics. Nat Commun. 2022 12 03; 13(1):7471. View Abstract
  13. Reflections on Integrins-Past, Present, and Future: The Albert Lasker Basic Medical Research Award. JAMA. 2022 10 04; 328(13):1291-1292. View Abstract
  14. Structures of VWF tubules before and after concatemerization reveal a mechanism of disulfide bond exchange. Blood. 2022 09 22; 140(12):1419-1430. View Abstract
  15. A general chemical principle for creating closure-stabilizing integrin inhibitors. Cell. 2022 09 15; 185(19):3533-3550.e27. View Abstract
  16. Dynamics of integrin a5ß1, fibronectin, and their complex reveal sites of interaction and conformational change. J Biol Chem. 2022 09; 298(9):102323. View Abstract
  17. Monomeric prefusion structure of an extremophile gamete fusogen and stepwise formation of the postfusion trimeric state. Nat Commun. 2022 07 13; 13(1):4064. View Abstract
  18. Von Willebrand factor A1 domain stability and affinity for GPIba are differentially regulated by its O-glycosylated N- and C-linker. Elife. 2022 05 09; 11. View Abstract
  19. Loss of LRRC33-Dependent TGFß1 Activation Enhances Antitumor Immunity and Checkpoint Blockade Therapy. Cancer Immunol Res. 2022 04 01; 10(4):453-467. View Abstract
  20. Regulation of integrin a5ß1 conformational states and intrinsic affinities by metal ions and the ADMIDAS. Mol Biol Cell. 2022 05 15; 33(6):ar56. View Abstract
  21. Protection of the Prodomain a1-Helix Correlates with Latency in the Transforming Growth Factor-ß Family. J Mol Biol. 2022 03 15; 434(5):167439. View Abstract
  22. Structural basis of malaria transmission blockade by a monoclonal antibody to gamete fusogen HAP2. Elife. 2021 12 23; 10. View Abstract
  23. Single-molecule imaging of von Willebrand factor reveals tension-dependent self-association. Blood. 2021 12 09; 138(23):2425-2434. View Abstract
  24. Low-affinity integrin states have faster ligand-binding kinetics than the high-affinity state. Elife. 2021 12 02; 10. View Abstract
  25. Complement Receptor 3 Forms a Compact High-Affinity Complex with iC3b. J Immunol. 2021 06 15; 206(12):3032-3042. View Abstract
  26. Disulfide exchange in multimerization of von Willebrand factor and gel-forming mucins. Blood. 2021 03 04; 137(9):1263-1267. View Abstract
  27. CD11c regulates hematopoietic stem and progenitor cells under stress. Blood Adv. 2020 12 22; 4(24):6086-6097. View Abstract
  28. Evolutionarily distant I domains can functionally replace the essential ligand-binding domain of Plasmodium TRAP. Elife. 2020 07 10; 9. View Abstract
  29. Design and assessment of TRAP-CSP fusion antigens as effective malaria vaccines. PLoS One. 2020; 15(1):e0216260. View Abstract
  30. General structural features that regulate integrin affinity revealed by atypical aVß8. Nat Commun. 2019 12 02; 10(1):5481. View Abstract
  31. Specific high affinity interaction of Helicobacter pylori CagL with integrin aV ß6 promotes type IV secretion of CagA into human cells. FEBS J. 2019 10; 286(20):3980-3997. View Abstract
  32. Electrostatic Steering Enables Flow-Activated Von Willebrand Factor to Bind Platelet Glycoprotein, Revealed by Single-Molecule Stretching and Imaging. J Mol Biol. 2019 03 29; 431(7):1380-1396. View Abstract
  33. The von Willebrand factor D'D3 assembly and structural principles for factor VIII binding and concatemer biogenesis. Blood. 2019 04 04; 133(14):1523-1533. View Abstract
  34. A Tandem Mass Spectrometry Sequence Database Search Method for Identification of O-Fucosylated Proteins by Mass Spectrometry. J Proteome Res. 2019 02 01; 18(2):652-663. View Abstract
  35. Fusion surface structure, function, and dynamics of gamete fusogen HAP2. Elife. 2018 10 03; 7. View Abstract
  36. A Milieu Molecule for TGF-ß Required for Microglia Function in the Nervous System. Cell. 2018 06 28; 174(1):156-171.e16. View Abstract
  37. Ligand- and cation-induced structural alterations of the leukocyte integrin LFA-1. J Biol Chem. 2018 04 27; 293(17):6565-6577. View Abstract
  38. Measuring Integrin Conformational Change on the Cell Surface with Super-Resolution Microscopy. Cell Rep. 2018 02 13; 22(7):1903-1912. View Abstract
  39. High integrin aVß6 affinity reached by hybrid domain deletion slows ligand-binding on-rate. Proc Natl Acad Sci U S A. 2018 02 13; 115(7):E1429-E1436. View Abstract
  40. Tolloid cleavage activates latent GDF8 by priming the pro-complex for dissociation. EMBO J. 2018 02 01; 37(3):384-397. View Abstract
  41. Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration. Nat Commun. 2017 12 11; 8(1):2047. View Abstract
  42. Energy landscape differences among integrins establish the framework for understanding activation. J Cell Biol. 2018 01 02; 217(1):397-412. View Abstract
  43. Prodomain-growth factor swapping in the structure of pro-TGF-ß1. J Biol Chem. 2018 02 02; 293(5):1579-1589. View Abstract
  44. Structural basis of regulation of von Willebrand factor binding to glycoprotein Ib. J Biol Chem. 2014 Feb 28; 289(9):5565-79. View Abstract
  45. An internal ligand-bound, metastable state of a leukocyte integrin, aXß2. J Cell Biol. 2013 Nov 25; 203(4):629-42. View Abstract
  46. How natalizumab binds and antagonizes a4 integrins. J Biol Chem. 2013 Nov 08; 288(45):32314-32325. View Abstract
  47. Complete integrin headpiece opening in eight steps. J Cell Biol. 2013 Jun 24; 201(7):1053-68. View Abstract
  48. Release of cellular tension signals self-restorative ventral lamellipodia to heal barrier micro-wounds. J Cell Biol. 2013 Apr 29; 201(3):449-65. View Abstract
  49. Mechanisms by which von Willebrand disease mutations destabilize the A2 domain. J Biol Chem. 2013 Mar 01; 288(9):6317-24. View Abstract
  50. Domain 1 of mucosal addressin cell adhesion molecule has an I1-set fold and a flexible integrin-binding loop. J Biol Chem. 2013 Mar 01; 288(9):6284-94. View Abstract
  51. Shape change in the receptor for gliding motility in Plasmodium sporozoites. Proc Natl Acad Sci U S A. 2012 Dec 26; 109(52):21420-5. View Abstract
  52. a(V)ß(3) integrin crystal structures and their functional implications. Biochemistry. 2012 Nov 06; 51(44):8814-28. View Abstract
  53. Mechanisms for kinase-mediated dimerization of the epidermal growth factor receptor. J Biol Chem. 2012 Nov 02; 287(45):38244-53. View Abstract
  54. Complex structure of engineered modular domains defining molecular interaction between ICAM-1 and integrin LFA-1. PLoS One. 2012; 7(8):e44124. View Abstract
  55. The RGD finger of Del-1 is a unique structural feature critical for integrin binding. FASEB J. 2012 Aug; 26(8):3412-20. View Abstract
  56. Unexpected fold in the circumsporozoite protein target of malaria vaccines. Proc Natl Acad Sci U S A. 2012 May 15; 109(20):7817-22. View Abstract
  57. Sequence and structure relationships within von Willebrand factor. Blood. 2012 Jul 12; 120(2):449-58. View Abstract
  58. Antigen recognition is facilitated by invadosome-like protrusions formed by memory/effector T cells. J Immunol. 2012 Apr 15; 188(8):3686-99. View Abstract
  59. Structure-guided design of a high-affinity platelet integrin aIIbß3 receptor antagonist that disrupts Mg²? binding to the MIDAS. Sci Transl Med. 2012 Mar 14; 4(125):125ra32. View Abstract
  60. Molecular basis for complement recognition by integrin aXß2. Proc Natl Acad Sci U S A. 2012 Mar 20; 109(12):4586-91. View Abstract
  61. Calcium stabilizes the von Willebrand factor A2 domain by promoting refolding. Proc Natl Acad Sci U S A. 2012 Mar 06; 109(10):3742-7. View Abstract
  62. GARP regulates the bioavailability and activation of TGFß. Mol Biol Cell. 2012 Mar; 23(6):1129-39. View Abstract
  63. Structural specializations of a(4)ß(7), an integrin that mediates rolling adhesion. J Cell Biol. 2012 Jan 09; 196(1):131-46. View Abstract
  64. Integrin inside-out signaling and the immunological synapse. Curr Opin Cell Biol. 2012 Feb; 24(1):107-15. View Abstract
  65. The C-terminal aI domain linker as a critical structural element in the conformational activation of aI integrins. J Biol Chem. 2011 Dec 09; 286(49):42115-42122. View Abstract
  66. Regulation of integrin affinity on cell surfaces. EMBO J. 2011 Sep 23; 30(23):4712-27. View Abstract
  67. A pH-regulated dimeric bouquet in the structure of von Willebrand factor. EMBO J. 2011 Aug 19; 30(19):4098-111. View Abstract
  68. Intact alphaIIbbeta3 integrin is extended after activation as measured by solution X-ray scattering and electron microscopy. J Biol Chem. 2011 Oct 07; 286(40):35218-26. View Abstract
  69. Simultaneous visualization of the extracellular and cytoplasmic domains of the epidermal growth factor receptor. Nat Struct Mol Biol. 2011 Aug 07; 18(9):984-9. View Abstract
  70. Biology and physics of von Willebrand factor concatamers. J Thromb Haemost. 2011 Jul; 9 Suppl 1:130-43. View Abstract
  71. Latent TGF-ß structure and activation. Nature. 2011 Jun 15; 474(7351):343-9. View Abstract
  72. Induction by IL 1 and interferon-?: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J. Immunol. 1986. 137: 245-254. J Immunol. 2011 May 01; 186(9):5024-33. View Abstract
  73. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J. Immunol. 1986. 137: 1270-1274. J Immunol. 2011 May 01; 186(9):5034-8. View Abstract
  74. A novel calcium-binding site of von Willebrand factor A2 domain regulates its cleavage by ADAMTS13. Blood. 2011 Apr 28; 117(17):4623-31. View Abstract
  75. Cation-pi interaction regulates ligand-binding affinity and signaling of integrin alpha4beta7. Proc Natl Acad Sci U S A. 2010 Dec 14; 107(50):21388-93. View Abstract
  76. Tests of integrin transmembrane domain homo-oligomerization during integrin ligand binding and signaling. J Biol Chem. 2011 Jan 21; 286(3):1860-7. View Abstract
  77. Structural evidence for loose linkage between ligand binding and kinase activation in the epidermal growth factor receptor. Mol Cell Biol. 2010 Nov; 30(22):5432-43. View Abstract
  78. A mechanically stabilized receptor-ligand flex-bond important in the vasculature. Nature. 2010 Aug 19; 466(7309):992-5. View Abstract
  79. Requirement of open headpiece conformation for activation of leukocyte integrin alphaXbeta2. Proc Natl Acad Sci U S A. 2010 Aug 17; 107(33):14727-32. View Abstract
  80. Closed headpiece of integrin aIIbß3 and its complex with an aIIbß3-specific antagonist that does not induce opening. Blood. 2010 Dec 02; 116(23):5050-9. View Abstract
  81. Modulation of integrin activation by an entropic spring in the {beta}-knee. J Biol Chem. 2010 Oct 22; 285(43):32954-32966. View Abstract
  82. Engineering of single Ig superfamily domain of intercellular adhesion molecule 1 (ICAM-1) for native fold and function. J Biol Chem. 2010 May 21; 285(21):15906-15. View Abstract
  83. Structure of an integrin with an alphaI domain, complement receptor type 4. EMBO J. 2010 Feb 03; 29(3):666-79. View Abstract
  84. Structural basis of activation-dependent binding of ligand-mimetic antibody AL-57 to integrin LFA-1. Proc Natl Acad Sci U S A. 2009 Oct 27; 106(43):18345-50. View Abstract
  85. Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand factor. Science. 2009 Jun 05; 324(5932):1330-4. View Abstract
  86. Structural specializations of A2, a force-sensing domain in the ultralarge vascular protein von Willebrand factor. Proc Natl Acad Sci U S A. 2009 Jun 09; 106(23):9226-31. View Abstract
  87. The structure of a receptor with two associating transmembrane domains on the cell surface: integrin alphaIIbbeta3. Mol Cell. 2009 Apr 24; 34(2):234-49. View Abstract
  88. The novel S527F mutation in the integrin beta3 chain induces a high affinity alphaIIbbeta3 receptor by hindering adoption of the bent conformation. J Biol Chem. 2009 May 29; 284(22):14914-20. View Abstract
  89. Structural basis for selectin mechanochemistry. Proc Natl Acad Sci U S A. 2009 Jan 06; 106(1):91-6. View Abstract
  90. Transmission of allostery through the lectin domain in selectin-mediated cell adhesion. Proc Natl Acad Sci U S A. 2009 Jan 06; 106(1):85-90. View Abstract
  91. Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces. Mol Cell. 2008 Dec 26; 32(6):849-61. View Abstract
  92. Rationally designed integrin beta3 mutants stabilized in the high affinity conformation. J Biol Chem. 2009 Feb 06; 284(6):3917-24. View Abstract
  93. Functional and structural stability of the epidermal growth factor receptor in detergent micelles and phospholipid nanodiscs. Biochemistry. 2008 Sep 30; 47(39):10314-23. View Abstract
  94. Structural basis for distinctive recognition of fibrinogen gammaC peptide by the platelet integrin alphaIIbbeta3. J Cell Biol. 2008 Aug 25; 182(4):791-800. View Abstract
  95. An unusual allosteric mobility of the C-terminal helix of a high-affinity alphaL integrin I domain variant bound to ICAM-5. Mol Cell. 2008 Aug 08; 31(3):432-7. View Abstract
  96. Trans-cellular migration: cell-cell contacts get intimate. Curr Opin Cell Biol. 2008 Oct; 20(5):533-40. View Abstract
  97. Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration. J Exp Med. 2008 Jan 21; 205(1):195-205. View Abstract
  98. Structural plasticity in Ig superfamily domain 4 of ICAM-1 mediates cell surface dimerization. Proc Natl Acad Sci U S A. 2007 Sep 25; 104(39):15358-63. View Abstract
  99. Specific and covalent labeling of a membrane protein with organic fluorochromes and quantum dots. Proc Natl Acad Sci U S A. 2007 Sep 11; 104(37):14753-8. View Abstract
  100. Binding between the integrin alphaXbeta2 (CD11c/CD18) and heparin. J Biol Chem. 2007 Oct 19; 282(42):30869-77. View Abstract
  101. The connection between metal ion affinity and ligand affinity in integrin I domains. Biochim Biophys Acta. 2007 Sep; 1774(9):1148-55. View Abstract
  102. Requirement of alpha and beta subunit transmembrane helix separation for integrin outside-in signaling. Blood. 2007 Oct 01; 110(7):2475-83. View Abstract
  103. Transcellular diapedesis is initiated by invasive podosomes. Immunity. 2007 Jun; 26(6):784-97. View Abstract
  104. Tests of the extension and deadbolt models of integrin activation. J Biol Chem. 2007 Apr 20; 282(16):11914-20. View Abstract
  105. Structural basis of integrin regulation and signaling. Annu Rev Immunol. 2007; 25:619-47. View Abstract
  106. Importance of force linkage in mechanochemistry of adhesion receptors. Biochemistry. 2006 Dec 19; 45(50):15020-8. View Abstract
  107. Structural transitions of complement component C3 and its activation products. Proc Natl Acad Sci U S A. 2006 Dec 26; 103(52):19737-42. View Abstract
  108. Complement and the multifaceted functions of VWA and integrin I domains. Structure. 2006 Nov; 14(11):1611-6. View Abstract
  109. A small molecule agonist of an integrin, alphaLbeta2. J Biol Chem. 2006 Dec 08; 281(49):37904-12. View Abstract
  110. Activation of leukocyte beta2 integrins by conversion from bent to extended conformations. Immunity. 2006 Oct; 25(4):583-94. View Abstract
  111. A high affinity human antibody antagonist of P-selectin mediated rolling. Biochem Biophys Res Commun. 2006 Nov 24; 350(3):508-13. View Abstract
  112. AL-57, a ligand-mimetic antibody to integrin LFA-1, reveals chemokine-induced affinity up-regulation in lymphocytes. Proc Natl Acad Sci U S A. 2006 Sep 19; 103(38):13991-6. View Abstract
  113. Regulation of outside-in signaling and affinity by the beta2 I domain of integrin alphaLbeta2. Proc Natl Acad Sci U S A. 2006 Aug 29; 103(35):13062-7. View Abstract
  114. Integrin structures and conformational signaling. Curr Opin Cell Biol. 2006 Oct; 18(5):579-86. View Abstract
  115. Identification and characterization of a human monoclonal antagonistic antibody AL-57 that preferentially binds the high-affinity form of lymphocyte function-associated antigen-1. J Leukoc Biol. 2006 Oct; 80(4):905-14. View Abstract
  116. Remodeling of the lectin-EGF-like domain interface in P- and L-selectin increases adhesiveness and shear resistance under hydrodynamic force. Nat Immunol. 2006 Aug; 7(8):883-9. View Abstract
  117. Immunoprecipitation. Curr Protoc Neurosci. 2006 May; Chapter 5:Unit 5.24. View Abstract
  118. Directed evolution to probe protein allostery and integrin I domains of 200,000-fold higher affinity. Proc Natl Acad Sci U S A. 2006 Apr 11; 103(15):5758-63. View Abstract
  119. Transition from rolling to firm adhesion can be mimicked by extension of integrin alphaLbeta2 in an intermediate affinity state. J Biol Chem. 2006 Apr 21; 281(16):10876-82. View Abstract
  120. Rational design of intercellular adhesion molecule-1 (ICAM-1) variants for antagonizing integrin lymphocyte function-associated antigen-1-dependent adhesion. J Biol Chem. 2006 Feb 24; 281(8):5042-9. View Abstract
  121. Two-dimensional kinetics regulation of alphaLbeta2-ICAM-1 interaction by conformational changes of the alphaL-inserted domain. J Biol Chem. 2005 Dec 23; 280(51):42207-18. View Abstract
  122. Disrupting integrin transmembrane domain heterodimerization increases ligand binding affinity, not valency or clustering. Proc Natl Acad Sci U S A. 2005 Mar 08; 102(10):3679-84. View Abstract
  123. An atomic resolution view of ICAM recognition in a complex between the binding domains of ICAM-3 and integrin alphaLbeta2. Proc Natl Acad Sci U S A. 2005 Mar 01; 102(9):3366-71. View Abstract
  124. Exposure of acidic residues as a danger signal for recognition of fibrinogen and other macromolecules by integrin alphaXbeta2. Proc Natl Acad Sci U S A. 2005 Feb 01; 102(5):1614-9. View Abstract
  125. The primacy of affinity over clustering in regulation of adhesiveness of the integrin {alpha}L{beta}2. J Cell Biol. 2004 Dec 20; 167(6):1241-53. View Abstract
  126. Conversion between three conformational states of integrin I domains with a C-terminal pull spring studied with molecular dynamics. Structure. 2004 Dec; 12(12):2137-47. View Abstract
  127. Contribution of N-linked glycans to the conformation and function of intercellular adhesion molecules (ICAMs). J Biol Chem. 2005 Feb 18; 280(7):5854-61. View Abstract
  128. A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them. J Cell Biol. 2004 Oct 25; 167(2):377-88. View Abstract
  129. The integrin alpha-subunit leg extends at a Ca2+-dependent epitope in the thigh/genu interface upon activation. Proc Natl Acad Sci U S A. 2004 Oct 26; 101(43):15422-7. View Abstract
  130. RIAM, an Ena/VASP and Profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion. Dev Cell. 2004 Oct; 7(4):585-95. View Abstract
  131. The relative influence of metal ion binding sites in the I-like domain and the interface with the hybrid domain on rolling and firm adhesion by integrin alpha4beta7. J Biol Chem. 2004 Dec 31; 279(53):55556-61. View Abstract
  132. Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics. Nature. 2004 Nov 04; 432(7013):59-67. View Abstract
  133. The binding sites for competitive antagonistic, allosteric antagonistic, and agonistic antibodies to the I domain of integrin LFA-1. J Immunol. 2004 Sep 15; 173(6):3972-8. View Abstract
  134. Integrin beta3 regions controlling binding of murine mAb 7E3: implications for the mechanism of integrin alphaIIbbeta3 activation. Proc Natl Acad Sci U S A. 2004 Sep 07; 101(36):13114-20. View Abstract
  135. A specific interface between integrin transmembrane helices and affinity for ligand. PLoS Biol. 2004 Jun; 2(6):e153. View Abstract
  136. Allosteric beta1 integrin antibodies that stabilize the low affinity state by preventing the swing-out of the hybrid domain. J Biol Chem. 2004 Jun 25; 279(26):27466-71. View Abstract
  137. Structural basis for dimerization of ICAM-1 on the cell surface. Mol Cell. 2004 Apr 23; 14(2):269-76. View Abstract
  138. Rolling adhesion through an extended conformation of integrin alphaLbeta2 and relation to alpha I and beta I-like domain interaction. Immunity. 2004 Apr; 20(4):393-406. View Abstract
  139. Boca-dependent maturation of beta-propeller/EGF modules in low-density lipoprotein receptor proteins. EMBO J. 2004 Mar 24; 23(6):1372-80. View Abstract
  140. Activation of integrin beta-subunit I-like domains by one-turn C-terminal alpha-helix deletions. Proc Natl Acad Sci U S A. 2004 Feb 24; 101(8):2333-8. View Abstract
  141. Intersubunit signal transmission in integrins by a receptor-like interaction with a pull spring. Proc Natl Acad Sci U S A. 2004 Mar 02; 101(9):2906-11. View Abstract
  142. The three-dimensional structure of integrins and their ligands, and conformational regulation of cell adhesion. Adv Protein Chem. 2004; 68:29-63. View Abstract
  143. Therapeutic antagonists and the conformational regulation of the beta2 integrins. Curr Top Med Chem. 2004; 4(14):1485-95. View Abstract
  144. Locking the beta3 integrin I-like domain into high and low affinity conformations with disulfides. J Biol Chem. 2004 Mar 12; 279(11):10215-21. View Abstract
  145. Endothelial cells proactively form microvilli-like membrane projections upon intercellular adhesion molecule 1 engagement of leukocyte LFA-1. J Immunol. 2003 Dec 01; 171(11):6135-44. View Abstract
  146. Bistable regulation of integrin adhesiveness by a bipolar metal ion cluster. Nat Struct Biol. 2003 Dec; 10(12):995-1001. View Abstract
  147. Integrin avidity regulation: are changes in affinity and conformation underemphasized? Curr Opin Cell Biol. 2003 Oct; 15(5):547-56. View Abstract
  148. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science. 2003 Sep 19; 301(5640):1720-5. View Abstract
  149. Structure of integrin alpha5beta1 in complex with fibronectin. EMBO J. 2003 Sep 15; 22(18):4607-15. View Abstract
  150. Small molecule integrin antagonists that bind to the beta2 subunit I-like domain and activate signals in one direction and block them in the other. Immunity. 2003 Sep; 19(3):391-402. View Abstract
  151. Therapeutic antagonists and conformational regulation of integrin function. Nat Rev Drug Discov. 2003 Sep; 2(9):703-16. View Abstract
  152. Overlapping and selective roles of endothelial intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 in lymphocyte trafficking. J Immunol. 2003 Sep 01; 171(5):2588-93. View Abstract
  153. Complex between nidogen and laminin fragments reveals a paradigmatic beta-propeller interface. Nature. 2003 Aug 21; 424(6951):969-74. View Abstract
  154. The critical cytoplasmic regions of the alphaL/beta2 integrin in Rap1-induced adhesion and migration. Mol Biol Cell. 2003 Jun; 14(6):2570-82. View Abstract
  155. Stabilizing the open conformation of the integrin headpiece with a glycan wedge increases affinity for ligand. Proc Natl Acad Sci U S A. 2003 Mar 04; 100(5):2403-8. View Abstract
  156. High affinity ligand binding by integrins does not involve head separation. J Biol Chem. 2003 May 09; 278(19):17185-9. View Abstract
  157. Structure and allosteric regulation of the alpha X beta 2 integrin I domain. Proc Natl Acad Sci U S A. 2003 Feb 18; 100(4):1873-8. View Abstract
  158. Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation. Cell. 2003 Jan 10; 112(1):99-111. View Abstract
  159. Stabilizing the integrin alpha M inserted domain in alternative conformations with a range of engineered disulfide bonds. Proc Natl Acad Sci U S A. 2002 Dec 24; 99(26):16737-41. View Abstract
  160. Predicted and experimental structures of integrins and beta-propellers. Curr Opin Struct Biol. 2002 Dec; 12(6):802-13. View Abstract
  161. Transition from rolling to firm adhesion is regulated by the conformation of the I domain of the integrin lymphocyte function-associated antigen-1. J Biol Chem. 2002 Dec 27; 277(52):50255-62. View Abstract
  162. Measurement of selectin tether bond lifetimes. Biophys J. 2002 Oct; 83(4):2318-20; author reply 2320-3. View Abstract
  163. Archaeal surface layer proteins contain beta propeller, PKD, and beta helix domains and are related to metazoan cell surface proteins. Structure. 2002 Oct; 10(10):1453-64. View Abstract
  164. Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling. Cell. 2002 Sep 06; 110(5):599-11. View Abstract
  165. Integrin activation and structural rearrangement. Immunol Rev. 2002 Aug; 186:141-63. View Abstract
  166. Chondroitin sulfate B exerts its inhibitory effect on secondary lymphoid tissue chemokine (SLC) by binding to the C-terminus of SLC. Biochim Biophys Acta. 2002 Jul 03; 1571(3):219-24. View Abstract
  167. César Milstein, the father of modern immunology. Nat Immunol. 2002 Jun; 3(6):501-3. View Abstract
  168. Immunology. Retrospective: César Milstein (1927-2002). Science. 2002 May 17; 296(5571):1253. View Abstract
  169. The role of the specificity-determining loop of the integrin beta subunit I-like domain in autonomous expression, association with the alpha subunit, and ligand binding. Biochemistry. 2002 Apr 02; 41(13):4339-47. View Abstract
  170. The genome of M. acetivorans reveals extensive metabolic and physiological diversity. Genome Res. 2002 Apr; 12(4):532-42. View Abstract
  171. Cysteine-rich module structure reveals a fulcrum for integrin rearrangement upon activation. Nat Struct Biol. 2002 Apr; 9(4):282-7. View Abstract
  172. Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus. Immunity. 2002 Feb; 16(2):205-18. View Abstract
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