1TJT

X-ray structure of the human alpha-actinin isoform 3 at 2.2A resolution

Summary for 1TJT

• Entry DOI: 10.2210/pdb1tjt/pdb
• Related: 1AOA 1DXX 1MB8 1QAG 1WKU
• Descriptor: Alpha-actinin 3 (2 entities in total)
• Functional Keywords: calponin homology domain, actin binding domain, contractile protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 28620.84

Authors

Franzot, G.,Sjoblom, B.,Gautel, M.,Djinovic Carugo, K. (deposition date: 2004-06-07, release date: 2005-05-17, Last modification date: 2023-10-25)

Primary citation

Franzot, G.,Sjoblom, B.,Gautel, M.,Djinovic Carugo, K.
The crystal structure of the actin binding domain from alpha-actinin in its closed conformation: structural insight into phospholipid regulation of alpha-actinin
J.Mol.Biol., 348:151-165, 2005

PubMed Abstract: 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.

PubMed: 15808860
DOI: 10.1016/j.jmb.2005.01.002

Experimental method

X-RAY DIFFRACTION (2.19 Å)