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1: J Biol Chem. 2004 Mar 12;279(11):10215-21. Epub 2003 Dec 16.
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Locking the beta3 integrin I-like domain into high and low affinity conformations with disulfides.

Luo BH, Takagi J, Springer TA.

CBR Institute fo Biomedical Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.

Although integrin alpha subunit I domains exist in multiple conformations, it is controversial whether integrin beta subunit I-like domains undergo structurally analogous movements of the alpha7-helix that are linked to affinity for ligand. Disulfide bonds were introduced into the beta(3) integrin I-like domain to lock its beta6-alpha7 loop and alpha7-helix in two distinct conformations. Soluble ligand binding, ligand mimetic mAb binding and cell adhesion studies showed that disulfide-bonded receptor alpha(IIb)beta(3)(T329C/A347C) was locked in a low affinity state, and dithiothreitol treatment restored the capability of being activated to high affinity binding; by contrast, disulfide-bonded alpha(IIb)beta(3)(V332C/M335C) was locked in a high affinity state. The results suggest that activation of the beta subunit I-like domain is analogous to that of the alpha subunit I domain, i.e. that axial movement in the C-terminal direction of the alpha7-helix is linked to rearrangement of the I-like domain metal ion-dependent adhesion site into a high affinity conformation.

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PMID: 14681220 [PubMed - indexed for MEDLINE]