1mf7
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INTEGRIN ALPHA M I DOMAIN
OverviewOverview
The alpha-I domain, found in the alpha-subunit of the leucocyte integrins, such as alphaMbeta2 and alphaLbeta2, switches between the open and closed, tertiary conformations, reflecting the high- and low-affinity, ligand-binding states of the integrin that are required for regulated cell, adhesion and migration. In the present study we show, by using point, mutations and engineered disulphide bonds, that ligand affinity can be, reduced or increased allosterically by altering the equilibrium between, the closed and open states. We determined equilibrium constants for the, binding of two ligands, fibrinogen and intercellular cell-adhesion, molecule 1, to the alphaM-I domain by surface plasmon resonance, and, determined crystal structures of a low-affinity mutant. Locking the domain, in the open conformation increases affinity by a factor of no greater than, 10, consistent with a closely balanced equilibrium between the two, conformations in the absence of ligand. This behaviour contrasts with that, of the unliganded alphaL-I domain, for which the equilibrium lies strongly, in favour of the closed conformation. These results suggest significant, differences in the way the parent integrins regulate I domain conformation, and hence ligand affinity.
About this StructureAbout this Structure
1MF7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Engineered allosteric mutants of the integrin alphaMbeta2 I domain: structural and functional studies., McCleverty CJ, Liddington RC, Biochem J. 2003 May 15;372(Pt 1):121-7. PMID:12611591
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