1bqs
From Proteopedia
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'''THE CRYSTAL STRUCTURE OF MUCOSAL ADDRESSIN CELL ADHESION MOLECULE-1 (MADCAM-1)''' | '''THE CRYSTAL STRUCTURE OF MUCOSAL ADDRESSIN CELL ADHESION MOLECULE-1 (MADCAM-1)''' | ||
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[[Category: Tan, K.]] | [[Category: Tan, K.]] | ||
[[Category: Wang, J H.]] | [[Category: Wang, J H.]] | ||
| - | [[Category: | + | [[Category: Cell adhesion glycoprotein]] |
| - | [[Category: | + | [[Category: Cell adhesion protein]] |
| - | [[Category: | + | [[Category: I-set fold]] |
| - | [[Category: | + | [[Category: Immunoglobulin fold]] |
| - | [[Category: | + | [[Category: Integrin recoginition]] |
| - | [[Category: | + | [[Category: Madcam-1]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:50:39 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 08:50, 2 May 2008
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. 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 Page seeded by OCA on Fri May 2 11:50:39 2008
