1mhp

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[[Image:1mhp.gif|left|200px]]
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{{Seed}}
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{{STRUCTURE_1mhp| PDB=1mhp | SCENE= }}
{{STRUCTURE_1mhp| PDB=1mhp | SCENE= }}
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'''Crystal structure of a chimeric alpha1 integrin I-domain in complex with the Fab fragment of a humanized neutralizing antibody'''
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===Crystal structure of a chimeric alpha1 integrin I-domain in complex with the Fab fragment of a humanized neutralizing antibody===
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==Overview==
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The alpha1beta1 (VLA-1) integrin is a cell-surface receptor for collagen and laminin and has been implicated in biological pathways involved in several pathological processes. These processes may be inhibited by the monoclonal antibody AQC2, which binds with high affinity to human alpha1beta1 integrin. To understand the structural basis of the inhibition we determined the crystal structure of the complex of a chimeric rat/human I domain of the alpha1beta1 integrin and the Fab fragment of humanized AQC2 antibody. The structure of the complex shows that the antibody blocks the collagen binding site of the I domain. An aspartate residue, from the CDR3 loop of the antibody heavy chain, coordinates the MIDAS metal ion in a manner similar to that of a glutamate residue from collagen. Substitution of the aspartate residue by alanine or arginine results in significant reduction of antibody binding affinity. Interestingly, although the mode of metal ion coordination resembles that of the open conformation, the I domain maintains an overall closed conformation previously observed only for unliganded I domains.
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(as it appears on PubMed at http://www.pubmed.gov), where 12662928 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12662928}}
==About this Structure==
==About this Structure==
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[[Category: Integrin]]
[[Category: Integrin]]
[[Category: Receptor]]
[[Category: Receptor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 01:03:07 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 23:59:10 2008''

Revision as of 20:59, 2 July 2008

Image:1mhp.png

Template:STRUCTURE 1mhp

Crystal structure of a chimeric alpha1 integrin I-domain in complex with the Fab fragment of a humanized neutralizing antibody

Template:ABSTRACT PUBMED 12662928

About this Structure

1MHP is a Single protein structure of sequence from Mus musculus and Rattus norvegicus. Full crystallographic information is available from OCA.

Reference

Crystal structure of the alpha1beta1 integrin I domain in complex with an antibody Fab fragment., Karpusas M, Ferrant J, Weinreb PH, Carmillo A, Taylor FR, Garber EA, J Mol Biol. 2003 Apr 11;327(5):1031-41. PMID:12662928

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