This proposal entitled 'Structure and interaction of IgSF and integrin families' is a continuation of my previous workssupported by the NIH grant HL48675. During the past funding period we have successfully carried out structuralstudies on ICAM-1, integrin aLp2, aiIBp3 and their interactions. In the next budget period, we will extend our structuralstudies to other ICAM family members (ICAM-3, -4 and -5) and their interactions with two leukocyte-specific p2integrins, the aLp2 and OM^, in order to investigate ICAM/p2 docking mechanism in general, their specificities, and howvarious ICAMs/p2 interactions specialize in different p2-associated biological settings. We will make efforts todecipher the IgSF/integrin interaction interface at high resolution, to obtain ternary complex structure of ICAM-1 withI domains from both aLp2 and OMP2. We will collaborate with Dr. Shimaoka to carry out structural investigation onmonoclonal antibodies that selectively bind high-affinity aL I domain, which should be of medical importance. We willcollaborate with Dr. Springer in structural studies on non-I-domain-containing integrins <x4p7 and/or 04^1 on leukocyteinteracting with their endothelial receptors MAdCAM-1 and/or VCAM-1. These are key to understand the adhesion.mechanism of leukocyte integrins in vascular biology. We have also started the study on another leukocyte-specificintegrin aEp? and its interaction with E-cadherin on epithelium to investigate E-cadherin's distinct integrin-bindingmechanism. We hope through these studies to compare different leukocyte integrin-binding mechanisms and explorethe specificity issue in leukocyte integrin-mediated cell-cell adhesion in the context of immunological significancesand potential medical applications.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Initial Review Group (HLBP)
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Immune Disease Institute, Inc.
United States
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