1m1u

From Proteopedia

Revision as of 11:50, 21 February 2008

AN ISOLEUCINE-BASED ALLOSTERIC SWITCH CONTROLS AFFINITY AND SHAPE SHIFTING IN INTEGRIN CD11B A-DOMAIN

Overview

In response to cell activation signals, integrins switch from a low to a high affinity state. Physiologic ligands bind to integrins through a von Willebrand Factor A-type domain. Crystallographic studies revealed two conformations of this domain, "closed" and "open." The latter crystallizes in complex with a pseudoligand or ligand, suggesting that it represents the high affinity state; data linking structure and activity are lacking however. In this communication, we expressed stable low and high affinity forms of integrin CD11b A-domain and determined their binding isotherms and crystal structures. The low affinity form, generated by deleting an N-terminal extension extrinsic to the domain, did not bind to physiologic ligands, and crystallized in the closed conformation. The high affinity form was generated by either deleting or substituting an invariable C-terminal Ile(316), wedged into a hydrophobic socket in the closed form, but displaced from it in the open structure. Both mutants crystallized in the open conformation, and the Ile(316) --> Gly-modified integrin displayed high affinity. Structural differences between the low and high affinity forms were detected in solution. These data establish the structure-function correlates for the CD11b A-domain, and define a ligand-independent isoleucine-based allosteric switch intrinsic to this domain that controls its conformation and affinity.

About this Structure

1M1U is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

Reference

An isoleucine-based allosteric switch controls affinity and shape shifting in integrin CD11b A-domain., Xiong JP, Li R, Essafi M, Stehle T, Arnaout MA, J Biol Chem. 2000 Dec 8;275(49):38762-7. PMID:11034990

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