2p28
From Proteopedia
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'''Structure of the PHE2 and PHE3 fragments of the integrin beta2 subunit''' | '''Structure of the PHE2 and PHE3 fragments of the integrin beta2 subunit''' | ||
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| + | ==Overview== | ||
| + | Integrins mediate cell adhesion in response to activation signals that trigger conformational changes within their ectodomain. It is thought that a compact bent conformation of the molecule represents its physiological low affinity state and extended conformations its active state. We have determined the structure of two integrin fragments of the beta2 subunit. The first structure, consisting of the plexin-semaphorin-integrin domain, hybrid, integrin-epidermal growth factor 1 (I-EGF1), and I-EGF2 domains (PHE2), showed an L-shaped conformation with the bend located between the I-EGF1 and I-EGF2 domains. The second structure, which includes, in addition, the I-EGF3 domain, showed an extended conformation. The major reorientation of I-EGF2 with respect to the other domains in the two structures is accompanied by a change of torsion angle of the disulfide bond between Cys(461)-Cys(492) by 180 degrees and the conversion of a short alpha-helix (residues Ser(468)-Cys(475)) into a flexible coil. Based on the PHE2 structure, we introduced a disulfide bond between the plexin-semaphorin-integrin domain and I-EGF2 domains in the beta2 subunit. The resultant alphaLbeta2 integrin (leukocyte function-associated antigen-1) variant was locked in a bent state and could not be detected with the monoclonal antibody KIM127 in Mg(2+)/EGTA. However, it retained the binding activity to ICAM-1. These results provide a structural hypothesis for our understanding of the transition between the resting and active states of leukocyte function-associated antigen-1. | ||
==About this Structure== | ==About this Structure== | ||
2P28 is a [[Protein complex]] structure of sequences 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=2P28 OCA]. | 2P28 is a [[Protein complex]] structure of sequences 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=2P28 OCA]. | ||
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| + | ==Reference== | ||
| + | A structural hypothesis for the transition between bent and extended conformations of the leukocyte beta2 integrins., Shi M, Foo SY, Tan SM, Mitchell EP, Law SK, Lescar J, J Biol Chem. 2007 Oct 12;282(41):30198-206. Epub 2007 Aug 1. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17673459 17673459] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: Integrin beta2 subunit]] | [[Category: Integrin beta2 subunit]] | ||
[[Category: Psi domain]] | [[Category: Psi domain]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 18 12:16:56 2008'' |
Revision as of 09:17, 18 June 2008
Structure of the PHE2 and PHE3 fragments of the integrin beta2 subunit
Overview
Integrins mediate cell adhesion in response to activation signals that trigger conformational changes within their ectodomain. It is thought that a compact bent conformation of the molecule represents its physiological low affinity state and extended conformations its active state. We have determined the structure of two integrin fragments of the beta2 subunit. The first structure, consisting of the plexin-semaphorin-integrin domain, hybrid, integrin-epidermal growth factor 1 (I-EGF1), and I-EGF2 domains (PHE2), showed an L-shaped conformation with the bend located between the I-EGF1 and I-EGF2 domains. The second structure, which includes, in addition, the I-EGF3 domain, showed an extended conformation. The major reorientation of I-EGF2 with respect to the other domains in the two structures is accompanied by a change of torsion angle of the disulfide bond between Cys(461)-Cys(492) by 180 degrees and the conversion of a short alpha-helix (residues Ser(468)-Cys(475)) into a flexible coil. Based on the PHE2 structure, we introduced a disulfide bond between the plexin-semaphorin-integrin domain and I-EGF2 domains in the beta2 subunit. The resultant alphaLbeta2 integrin (leukocyte function-associated antigen-1) variant was locked in a bent state and could not be detected with the monoclonal antibody KIM127 in Mg(2+)/EGTA. However, it retained the binding activity to ICAM-1. These results provide a structural hypothesis for our understanding of the transition between the resting and active states of leukocyte function-associated antigen-1.
About this Structure
2P28 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
A structural hypothesis for the transition between bent and extended conformations of the leukocyte beta2 integrins., Shi M, Foo SY, Tan SM, Mitchell EP, Law SK, Lescar J, J Biol Chem. 2007 Oct 12;282(41):30198-206. Epub 2007 Aug 1. PMID:17673459 Page seeded by OCA on Wed Jun 18 12:16:56 2008
