2RPN

A crucial role for high intrinsic specificity in the function of yeast SH3 domains

2RPN の概要

• エントリーDOI: 10.2210/pdb2rpn/pdb
• 分子名称: Actin-binding protein, Actin-regulating kinase 1 (2 entities in total)
• 機能のキーワード: sh3 domain, extended peptide, 3-10 helix, acetylation, actin-binding, cytoplasm, cytoskeleton, phosphoprotein, structural protein
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton, actin patch: P15891 P53974
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 8721.61

構造登録者

Stollar, E.J.,Garcia, B.,Chong, A.,Forman-Kay, J.,Davidson, A. (登録日: 2008-06-12, 公開日: 2009-06-16, 最終更新日: 2024-05-29)

主引用文献

Stollar, E.J.,Garcia, B.,Chong, P.A.,Rath, A.,Lin, H.,Forman-Kay, J.D.,Davidson, A.R.
Structural, functional, and bioinformatic studies demonstrate the crucial role of an extended peptide binding site for the SH3 domain of yeast Abp1p
J.Biol.Chem., 284:26918-26927, 2009

PubMed Abstract: SH3 domains, which are among the most frequently occurring protein interaction modules in nature, bind to peptide targets ranging in length from 7 to more than 25 residues. Although the bulk of studies on the peptide binding properties of SH3 domains have focused on interactions with relatively short peptides (less than 10 residues), a number of domains have been recently shown to require much longer sequences for optimal binding affinity. To gain greater insight into the binding mechanism and biological importance of interactions between an SH3 domain and extended peptide sequences, we have investigated interactions of the yeast Abp1p SH3 domain (AbpSH3) with several physiologically relevant 17-residue target peptide sequences. To obtain a molecular model for AbpSH3 interactions, we solved the structure of the AbpSH3 bound to a target peptide from the yeast actin patch kinase, Ark1p. Peptide target complexes from binding partners Scp1p and Sjl2p were also characterized, revealing that the AbpSH3 uses a common extended interface for interaction with these peptides, despite K(d) values for these peptides ranging from 0.3 to 6 mum. Mutagenesis studies demonstrated that residues across the whole 17-residue binding site are important both for maximal in vitro binding affinity and for in vivo function. Sequence conservation analysis revealed that both the AbpSH3 and its extended target sequences are highly conserved across diverse fungal species as well as higher eukaryotes. Our data imply that the AbpSH3 must bind extended target sites to function efficiently inside the cell.

PubMed: 19590096
DOI: 10.1074/jbc.M109.028431

実験手法

SOLUTION NMR