1bqs
From Proteopedia
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THE CRYSTAL STRUCTURE OF MUCOSAL ADDRESSIN CELL ADHESION MOLECULE-1 (MADCAM-1)
Overview
BACKGROUND: Mucosal addressin cell adhesion molecule 1 (MAdCAM-1) is a, cell adhesion molecule that is expressed on the endothelium in mucosa, and, guides the specific homing of lymphocytes into mucosal tissues. MAdCAM-1, belongs to a subclass of the immunoglobulin superfamily (IgSF), the, members of which are ligands for integrins. Human MAdCAM-1 has a unique, dual function compared to other members in the same subclass in that it, binds both the integrin alpha4beta7, through its two IgSF domains, and a, selectin expressed on leukocytes, via carbohydrate sidechains. The, structure determination of the two IgSF domains and comparison to the, N-terminal two-domain structures of vascular cell adhesion molecule 1, (VCAM-1) and intercellular adhesion molecules (ICAM-1 and ICAM-2) allow us, to assess the molecular basis of the interactions between integrins and, their preferred ligands. RESULTS: The crystal structure of a fragment, containing the two IgSF domains of human MAdCAM-1 has been determined to, 2.2 A resolution. The structure of MAdCAM-1 reveals two separate, integrin-recognition motifs. The key integrin-binding residue, Asp42, resides in the CD loop of domain 1; a buried arginine residue (Arg70), plays a critical role in maintaining the conformation of this loop. The, second binding site is associated with an unusual long D strand in domain, 2. The D and E strands extend beyond the main body of the domain, forming, a negatively charged beta ribbon unique to MAdCAM-1. This ribbon is, located on the same face as the key aspartate residue in domain 1, consistent with evidence that it is involved in integrin binding., CONCLUSIONS: The structural comparison of MAdCAM-1 to other members of the, same IgSF subclass reveals some interesting features. Firstly, MAdCAM-1, like VCAM-1, has the key integrin-binding residue located on the, protruding CD loop of domain 1 and binds to an integrin that lacks an I, domain. This is in contrast to ICAM-1 and ICAM-2 where the key residue is, located at the end of the C strand on a flat surface and which bind to, integrins that contain I domains. Secondly, architectural differences in, the CD loops of MAdCAM-1 and VCAM-1 cause an 8 A shift in position of the, critical aspartate residue, and may partly determine their binding, preference for different integrins. Finally, the unusual charge, distribution of the two-domain fragment of MAdCAM-1 is predicted to orient, the molecule optimally for integrin binding on the top of its long, mucin-like stalk.
About this Structure
1BQS is a Single protein structure of sequence from Homo sapiens with NDG as ligand. Full crystallographic information is available from OCA.
Reference
The structure of immunoglobulin superfamily domains 1 and 2 of MAdCAM-1 reveals novel features important for integrin recognition., Tan K, Casasnovas JM, Liu JH, Briskin MJ, Springer TA, Wang JH, Structure. 1998 Jun 15;6(6):793-801. PMID:9655832
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