1tjt
From Proteopedia
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| , resolution 2.19Å | |||||||
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| Gene: | ACTN3 (Homo sapiens) | ||||||
| Related: | 1AOA, 1DXX, 1MB8, 1QAG, 1WKU
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
X-ray structure of the human alpha-actinin isoform 3 at 2.2A resolution
Contents |
Overview
Alpha-actinin is the major F-actin crosslinking protein in both muscle and non-muscle cells. We report the crystal structure of the actin binding domain of human muscle alpha-actinin-3, which is formed by two consecutive calponin homology domains arranged in a "closed" conformation. Structural studies and available biochemical data on actin binding domains suggest that two calponin homology domains come in a closed conformation in the native apo-form, and that conformational changes involving the relative orientation of the two calponin homology domains are required for efficient binding to actin filaments. The actin binding activity of muscle isoforms is supposed to be regulated by phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), which binds to the second calponin homology domain. On the basis of structural analysis we propose a distinct binding site for PtdIns(4,5)P2, where the fatty acid moiety would be oriented in a direction that allows it to interact with the linker sequence between the actin binding domain and the first spectrin-like repeat, regulating thereby the binding of the C-terminal calmodulin-like domain to this linker.
Disease
Known disease associated with this structure: Alpha-actinin-3 deficiency OMIM:[102574], Sprinting performance OMIM:[102574]
About this Structure
1TJT is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The crystal structure of the actin binding domain from alpha-actinin in its closed conformation: structural insight into phospholipid regulation of alpha-actinin., Franzot G, Sjoblom B, Gautel M, Djinovic Carugo K, J Mol Biol. 2005 Apr 22;348(1):151-65. PMID:15808860
Page seeded by OCA on Sun Mar 30 23:57:01 2008
