3hi6

Crystal structure of intermediate affinity I domain of integrin LFA-1 with the Fab fragment of its antibody AL-57

spinqualitylabelsall models 3hi6, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3hi6 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MN, SO4 Related: 3hi5 Gene: CD11A, ITGAL, LFA-1 (Homo sapiens) Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The activity of integrin LFA-1 (alpha(L)beta(2)) to its ligand ICAM-1 is regulated through the conformational changes of its ligand-binding domain, the I domain of alpha(L) chain, from an inactive, low-affinity closed form (LA), to an intermediate-affinity form (IA), and then finally, to a high-affinity open form (HA). A ligand-mimetic human monoclonal antibody AL-57 (activated LFA-1 clone 57) was identified by phage display to specifically recognize the affinity-upregulated I domain. Here, we describe the crystal structures of the Fab fragment of AL-57 in complex with IA, as well as in its unligated form. We discuss the structural features conferring AL-57's strong selectivity for the high affinity, open conformation of the I domain. The AL-57-binding site overlaps the ICAM-1 binding site on the I domain. Furthermore, an antibody Asp mimics an ICAM Glu by forming a coordination to the metal-ion dependent adhesion site (MIDAS). The structure also reveals better shape complementarity and a more hydrophobic interacting interface in AL-57 binding than in ICAM-1 binding. The results explain AL-57's antagonistic mimicry of LFA-1's natural ligands, the ICAM molecules. Structural basis of activation-dependent binding of ligand-mimetic antibody AL-57 to integrin LFA-1.,Zhang H, Liu JH, Yang W, Springer T, Shimaoka M, Wang JH Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18345-50. Epub 2009 Sep 23. PMID:19805116 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody Integrin Introduction to Evolutionary Conservation Introduction to Evolutionary Conservation (Spanish)

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