Molecular recognition of the tes LIM2–3 domains by the actin-related protein arp7A
Boëda, B. and Knowles, P.P. and Briggs, David C. and Murray-Rust, J. and Soriano, E. and Garvalov, B.K. and McDonald, Neil Q. and Way, M. (2011) Molecular recognition of the tes LIM2–3 domains by the actin-related protein arp7A. Journal of Biological Chemistry 286 (13), pp. 11543-11554. ISSN 0021-9258.
Actin-related proteins (Arps) are a highly conserved family of proteins that have extensive sequence and structural similarity to actin. All characterized Arps are components of large multimeric complexes associated with chromatin or the cytoskeleton. In addition, the human genome encodes five conserved but largely uncharacterized “orphan” Arps, which appear to be mostly testis-specific. Here we show that Arp7A, which has 43% sequence identity with β-actin, forms a complex with the cytoskeletal proteins Tes and Mena in the subacrosomal layer of round spermatids. The N-terminal 65-residue extension to the actin-like fold of Arp7A interacts directly with Tes. The crystal structure of the 1–65Arp7A·LIM2–3Tes·EVH1Mena complex reveals that residues 28–49 of Arp7A contact the LIM2–3 domains of Tes. Two alanine residues from Arp7A that occupy equivalent apolar pockets in both LIM domains as well as an intervening GPAK linker that binds the LIM2–3 junction are critical for the Arp7A-Tes interaction. Equivalent occupied apolar pockets are also seen in the tandem LIM domain structures of LMO4 and Lhx3 bound to unrelated ligands. Our results indicate that apolar pocket interactions are a common feature of tandem LIM domain interactions, but ligand specificity is principally determined by the linker sequence.
|Additional Information:||This research was originally published in The Journal of Biological Chemistry. Batiste Boëda, Phillip P. Knowles, David C. Briggs, Judith Murray-Rust, Erika Soriano, Boyan K. Garvalov, Neil Q. McDonald and Michael Way. Molecular recognition of the tes LIM2–3 domains by the actin-related protein arp7A. The Journal of Biological Chemistry. 2011; 286(13):11543-11554. © The American Society for Biochemistry and Molecular Biology License information: http://creativecommons.org/licenses/by-nc/3.0/|
|Keyword(s) / Subject(s):||actin, cytoskeleton, protein domains, protein structure, protein-protein interactions, spermatogenesis, actin-related protein, LIM domain, testis|
|School:||Birkbeck Schools and Departments > School of Science > Biological Sciences|
|Research Centre:||Structural Molecular Biology, Institute of (ISMB)|
|Depositing User:||Sarah Hall|
|Date Deposited:||21 Jun 2012 10:42|
|Last Modified:||06 Dec 2016 10:43|
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