1MHP: Crystal Structure of a Chimeric Alpha1 Integrin I-domain in Complex With the FAB Fragment of a Humanized Neutralizing Antibody

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.
PDB ID: 1MHPDownload
MMDB ID: 22625
PDB Deposition Date: 2002/8/20
Updated in MMDB: 2007/10 
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Rattus norvegicus
Similar Structures:
Biological Unit for 1MHP: trimeric; determined by author and by software (PISA)
Molecular Components in 1MHP
Label Count Molecule
Proteins (3 molecules)
Integrin Alpha 1, (Residues 169-360)
Molecule annotation
FAB Fragment, Heavy Chain
Molecule annotation
FAB Fragment, Light Chain
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB