1M1U

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

Summary for 1M1U

• Entry DOI: 10.2210/pdb1m1u/pdb
• Related: 1IDO 1M1X
• Descriptor: Integrin alpha-M, CALCIUM ION (3 entities in total)
• Functional Keywords: integrin, cell adhesion protein, glycoprotein, a-domain, cd11b, cell adhesion
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P11215
• Total number of polymer chains: 1
• Total formula weight: 22301.39

Authors

Xiong, J.-P.,Li, R.,Essafi, M.,Stehle, T.,Arnaout, M.A. (deposition date: 2002-06-20, release date: 2002-08-07, Last modification date: 2024-02-14)

Primary citation

Xiong, J.P.,Li, R.,Essafi, M.,Stehle, T.,Arnaout, M.A.
An isoleucine-based allosteric switch controls affinity and shape shifting in integrin CD11b A-domain.
J.Biol.Chem., 275:38762-38767, 2000

PubMed Abstract: 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.

PubMed: 11034990
DOI: 10.1074/jbc.C000563200

Experimental method

X-RAY DIFFRACTION (2.3 Å)