Abstract

This proposal entitled """"""""Structure and interaction of IgSF and integrin families"""""""" is a continuation of my previous works supported by the NIH grant HL48675. During the past funding period we have successfully carried out structural studies on ICAM-1, integrin aLp2,aiIBp3 and their interactions. In the next budget period, we will extend our structural studies to other ICAM family members (ICAM-3, -4 and -5) and their interactions with two leukocyte-specific p2 integrins, the aLp2 and OM^, in order to investigate ICAM/p2 docking mechanism in general, their specificities, and how various ICAMs/p2 interactions specialize in different p2-associated biological settings. We will make efforts to decipher the IgSF/integrin interaction interface at high resolution, to obtain ternary complex structure of ICAM-1 with I domains from both aLp2 and OMP2. We will collaborate with Dr. Shimaoka to carry out structural investigation on monoclonal antibodies that selectively bind high-affinity aL I domain, which should be of medical importance. We will collaborate with Dr. Springer in structural studies on non-I-domain-containing integrins

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL048675-17
Application #
7916734
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
17
Fiscal Year
2009
Total Cost
$663,839
Indirect Cost

  Institution

Name
Immune Disease Institute, Inc.
Department
Type
DUNS #
059709394
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Finci, L; Zhang, Y; Meijers, R et al. (2015) Signaling mechanism of the netrin-1 receptor DCC in axon guidance. Prog Biophys Mol Biol 118:153-60
Jiang, Jian-kang; McCoy, Joshua G; Shen, Min et al. (2014) A novel class of ion displacement ligands as antagonists of the ?IIb?3 receptor that limit conformational reorganization of the receptor. Bioorg Med Chem Lett 24:1148-53
Liu, Ying; Zhang, Yan; Wang, Jia-Huai (2014) Crystal structure of human Ankyrin G death domain. Proteins 82:3476-82
Finci, Lorenzo I; Krüger, Nina; Sun, Xiaqin et al. (2014) The crystal structure of netrin-1 in complex with DCC reveals the bifunctionality of netrin-1 as a guidance cue. Neuron 83:839-849
Chen, Qiang; Sun, Xiaqin; Zhou, Xiao-hong et al. (2013) N-terminal horseshoe conformation of DCC is functionally required for axon guidance and might be shared by other neural receptors. J Cell Sci 126:186-95
Wang, Jia-Huai (2013) The sequence signature of an Ig-fold. Protein Cell 4:569-72
Xu, Amy J; Springer, Timothy A (2013) Mechanisms by which von Willebrand disease mutations destabilize the A2 domain. J Biol Chem 288:6317-24
Wang, Jia-huai; Reinherz, Ellis L (2012) The structural basis of ?? T-lineage immune recognition: TCR docking topologies, mechanotransduction, and co-receptor function. Immunol Rev 250:102-19
Yu, Yamei; Zhu, Jianghai; Mi, Li-Zhi et al. (2012) Structural specializations of ?(4)?(7), an integrin that mediates rolling adhesion. J Cell Biol 196:131-46
Xu, Amy J; Springer, Timothy A (2012) Calcium stabilizes the von Willebrand factor A2 domain by promoting refolding. Proc Natl Acad Sci U S A 109:3742-7

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