1mb8
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1mb8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mb8 OCA], [http://www.ebi.ac.uk/pdbsum/1mb8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1mb8 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Plectin is a widely expressed cytoskeletal linker. Here we report the crystal structure of the actin binding domain of plectin and show that this region is sufficient for interaction with F-actin or the cytoplasmic region of integrin alpha6beta4. The structure is formed by two calponin homology domains arranged in a closed conformation. We show that binding to F-actin induces a conformational change in plectin that is inhibited by an engineered interdomain disulfide bridge. A two-step induced fit mechanism involving binding and subsequent domain rearrangement is proposed. In contrast, interaction with integrin alpha6beta4 occurs in a closed conformation. Competitive binding of plectin to F-actin and integrin alpha6beta4 may rely on the observed alternative binding mechanisms and involve both allosteric and steric factors. | Plectin is a widely expressed cytoskeletal linker. Here we report the crystal structure of the actin binding domain of plectin and show that this region is sufficient for interaction with F-actin or the cytoplasmic region of integrin alpha6beta4. The structure is formed by two calponin homology domains arranged in a closed conformation. We show that binding to F-actin induces a conformational change in plectin that is inhibited by an engineered interdomain disulfide bridge. A two-step induced fit mechanism involving binding and subsequent domain rearrangement is proposed. In contrast, interaction with integrin alpha6beta4 occurs in a closed conformation. Competitive binding of plectin to F-actin and integrin alpha6beta4 may rely on the observed alternative binding mechanisms and involve both allosteric and steric factors. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Epidermolysis bullosa simplex, Ogna type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601282 601282]], Muscular dystrophy with epidermolysis bullosa simplex OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601282 601282]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: integrin beta4 hemidesmosome]] | [[Category: integrin beta4 hemidesmosome]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:13:55 2008'' |
Revision as of 19:13, 30 March 2008
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| , resolution 2.15Å | |||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of the actin binding domain of plectin
Overview
Plectin is a widely expressed cytoskeletal linker. Here we report the crystal structure of the actin binding domain of plectin and show that this region is sufficient for interaction with F-actin or the cytoplasmic region of integrin alpha6beta4. The structure is formed by two calponin homology domains arranged in a closed conformation. We show that binding to F-actin induces a conformational change in plectin that is inhibited by an engineered interdomain disulfide bridge. A two-step induced fit mechanism involving binding and subsequent domain rearrangement is proposed. In contrast, interaction with integrin alpha6beta4 occurs in a closed conformation. Competitive binding of plectin to F-actin and integrin alpha6beta4 may rely on the observed alternative binding mechanisms and involve both allosteric and steric factors.
About this Structure
1MB8 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural and functional analysis of the actin binding domain of plectin suggests alternative mechanisms for binding to F-actin and integrin beta4., Garcia-Alvarez B, Bobkov A, Sonnenberg A, de Pereda JM, Structure. 2003 Jun;11(6):615-25. PMID:12791251
Page seeded by OCA on Sun Mar 30 22:13:55 2008
