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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3513-3520. Prepublished online as a Blood First Edition Paper on December 14, 2006; DOI 10.1182/blood-2005-11-056689. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2005-11-056689v1 109/8/3513    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gupta, V. Articles by Amin Arnaout, M. Search for Related Content PubMed PubMed Citation Articles by Gupta, V. Articles by Amin Arnaout, M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Cytoskeleton Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES The ß-tail domain (ßTD) regulates physiologic ligand binding to integrin CD11b/CD18 Vineet Gupta1, Annette Gylling1, José Luis Alonso1, Takashi Sugimori1, Petre Ianakiev1, Jiang-Ping Xiong1, and M. Amin Arnaout1 1 Nephrology Division, Leukocyte Biology & Inflammation Program, Structural Biology Program, Massachusetts General Hospital, Harvard Medical School, Charlestown Crystallographic and electron microscopy studies revealed genuflexed (bent) integrins in both unliganded (inactive) and physiologic ligandbound (active) states, suggesting that local conformational changes are sufficient for activation. Herein we have explored the role of local changes in the contact region between the membrane-proximal ß-tail domain (ßTD) and the ligand-binding ßA domain of the bent conformation in regulating interaction of integrin CD11b/CD18 (Mß2) with its physiologic ligand iC3b. We replaced the ßTD CD loop residues D658GMD of the CD18 (ß2) subunit with the equivalent D672SSG of the ß3 subunit, with AGAA or with NGTD, expressed the respective heterodimeric receptors either transiently in epithelial HEK293T cells or stably in leukocytes (K562), and measured their ability to bind iC3b and to conformation-sensitive mAbs. In the presence of the physiologic divalent cations Ca2+ plus Mg2+ (at 1 mM each), the modified integrins showed increased (in HEK293) or constitutive (in K562) binding to iC3b compared with wild-type receptors. K562 expressing the ßTD-modified integrins bound in Ca2+Mg2+ to the ßA-directed high-affinity reporter mAb 24 but not to mAb KIM127, a reporter of the genu-straightened state. These data identify a role for the membrane proximal ßTD as an allosteric modulator of integrin activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Blood orchestrates a leukocyte integrin trio Joel S. Bennett Blood 2007 109: 3137-3138. [Full Text] [PDF] This article has been cited by other articles: J.-P. Xiong, B. Mahalingham, J. L. Alonso, L. A. Borrelli, X. Rui, S. Anand, B. T. Hyman, T. Rysiok, D. Muller-Pompalla, S. L. Goodman, et al. Crystal structure of the complete integrin {alpha}V{beta}3 ectodomain plus an {alpha}/{beta} transmembrane fragment J. Cell Biol., August 24, 2009; 186(4): 589 - 600. [Abstract] [Full Text] [PDF]

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