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Structures of the Phactr1 RPEL domain and RPEL motif complexes with G-Actin reveal the molecular basis for Actin Binding Cooperativity

Mouilleron, S. and Wiezlak, M. and O’Reilly, N. and Treisman, R. and McDonald, Neil Q. (2012) Structures of the Phactr1 RPEL domain and RPEL motif complexes with G-Actin reveal the molecular basis for Actin Binding Cooperativity. Structure 20 (11), pp. 1960-1970. ISSN 0969-2126.

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Official URL: http://dx.doi.org/10.1016/j.str.2012.08.031

Abstract

The Phactr family of PP1-binding proteins and the myocardin-related transcription factor family of transcriptional coactivators contain regulatory domains comprising three copies of the RPEL motif, a G-actin binding element. We report the structure of a Phactr1 G-actin⋅RPEL domain complex. Three G-actins surround the crank-shaped RPEL domain forming a closed helical assembly. Their spatial relationship is identical to the RPEL-actins within the pentavalent MRTF G-actin⋅RPEL domain complex, suggesting that conserved cooperative interactions between actin⋅RPEL units organize the assembly. In the trivalent Phactr1 complex, each G-actin⋅RPEL unit makes secondary contacts with its downstream actin involving distinct RPEL residues. Similar secondary contacts are seen in G-actin⋅RPEL peptide crystals. Loss-of-secondary-contact mutations destabilize the Phactr1 G-actin⋅RPEL assembly. Furthermore, actin-mediated inhibition of Phactr1 nuclear import requires secondary contact residues in the Phactr1 N-terminal RPEL-N motif, suggesting that it involves interaction of RPEL-N with the C-terminal assembly. Secondary actin contacts by actin-bound RPEL motifs thus govern formation of multivalent actin⋅RPEL assemblies.

Item Type: Article
School or Research Centre: Birkbeck Schools and Research Centres > School of Science > Biological Sciences
Depositing User: Administrator
Date Deposited: 18 Oct 2012 11:22
Last Modified: 08 May 2013 08:54
URI: http://eprints.bbk.ac.uk/id/eprint/5303

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