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dc.contributor.authorZhang, Hongmin
dc.contributor.authorLiu, Jin-huan
dc.contributor.authorYang, Wei
dc.contributor.authorSpringer, Timothy
dc.contributor.authorShimaoka, Motomu
dc.contributor.authorWang, Jia-huai
dc.date.accessioned2019-10-17T05:19:13Z
dc.date.issued2009
dc.identifier.citationZhang, H., J.-h. Liu, W. Yang, T. Springer, M. Shimaoka, and J.-h. Wang. 2009. “Structural Basis of Activation-Dependent Binding of Ligand-Mimetic Antibody AL-57 to Integrin LFA-1.” Proceedings of the National Academy of Sciences 106 (43). Proceedings of the National Academy of Sciences: 18345–50. doi:10.1073/pnas.0909301106.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41555775*
dc.description.abstractThe 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.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleStructural basis of activation-dependent binding of ligand-mimetic antibody AL-57 to integrin LFA-1
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorWang, Jia-Huai::0ea01606c2ad0a55493be0a19705594c::600
dc.date.available2019-10-17T05:19:13Z
dash.workflow.comments1Science Serial ID 90455
dc.identifier.doi10.1073/pnas.0909301106
dash.source.volume106;43
dash.source.page18345


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