1na5
From Proteopedia
(New page: 200px<br /> <applet load="1na5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1na5, resolution 1.50Å" /> '''INTEGRIN ALPHA M I ...) |
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| - | [[Image:1na5.gif|left|200px]]<br /> | + | [[Image:1na5.gif|left|200px]]<br /><applet load="1na5" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1na5" size=" | + | |
caption="1na5, resolution 1.50Å" /> | caption="1na5, resolution 1.50Å" /> | ||
'''INTEGRIN ALPHA M I DOMAIN'''<br /> | '''INTEGRIN ALPHA M I DOMAIN'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The alpha-I domain, found in the alpha-subunit of the leucocyte integrins | + | 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 Structure== | ==About this Structure== | ||
| - | 1NA5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1NA5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NA5 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Liddington, R | + | [[Category: Liddington, R C.]] |
| - | [[Category: McCleverty, C | + | [[Category: McCleverty, C J.]] |
[[Category: rossmann fold]] | [[Category: rossmann fold]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:03:53 2008'' |
Revision as of 12:03, 21 February 2008
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INTEGRIN ALPHA M I DOMAIN
Overview
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 Structure
1NA5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 14:03:53 2008
