1JMQ

YAP65 (L30K mutant) WW domain in Complex with GTPPPPYTVG peptide

1JMQ の概要

• エントリーDOI: 10.2210/pdb1jmq/pdb
• 関連するPDBエントリー: 1e0m 1eg4 1i5h
• 分子名称: 65 KDA YES-ASSOCIATED PROTEIN, WW Domain Binding Protein-1 (2 entities in total)
• 機能のキーワード: ww domain, polyproline ligand, yap65 mutant, structural protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P46937
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 6345.11

構造登録者

Pires, J.R.,Taha-Nejad, F.,Toepert, F.,Ast, T.,Hoffmuller, U.,Schneider-Mergener, J.,Kuhne, R.,Macias, M.J.,Oschkinat, H. (登録日: 2001-07-19, 公開日: 2001-12-21, 最終更新日: 2024-05-22)

主引用文献

Pires, J.R.,Taha-Nejad, F.,Toepert, F.,Ast, T.,Hoffmuller, U.,Schneider-Mergener, J.,Kuhne, R.,Macias, M.J.,Oschkinat, H.
Solution structures of the YAP65 WW domain and the variant L30 K in complex with the peptides GTPPPPYTVG, N-(n-octyl)-GPPPY and PLPPY and the application of peptide libraries reveal a minimal binding epitope.
J.Mol.Biol., 314:1147-1156, 2001

PubMed Abstract: The single mutation L30 K in the Hu-Yap65 WW domain increased the stability of the complex with the peptide GTPPPPYTVG (K(d)=40(+/-5) microM). Here we report the refined solution structure of this complex by NMR spectroscopy and further derived structure-activity relationships by using ligand peptide libraries with truncated sequences and a substitution analysis that yielded acetyl-PPPPY as the smallest high-affinity binding peptide (K(d)=60 microM). The structures of two new complexes with weaker binding ligands chosen based on these results (N-(n-octyl)-GPPPYNH(2) and Ac-PLPPY) comprising the wild-type WW domain of Hu-Yap65 were determined. Comparison of the structures of the three complexes were useful for identifying the molecular basis of high-affinity: hydrophobic and specific interactions between the side-chains of Y28 and W39 and P5' and P4', respectively, and hydrogen bonds between T37 (donnor) and P5' (acceptor) and between W39 (donnor) and T2' (acceptor) stabilize the complex.The structure of the complex L30 K Hu-Yap65 WW domain/GTPPPPYTVG is compared to the published crystal structure of the dystrophin WW domain bound to a segment of the beta-dystroglycan protein and to the solution structure of the first Nedd4 WW domain and its prolin-rich ligand, suggesting that WW sequences bind proline-rich peptides in an evolutionary conserved fashion. The position equivalent to T22 in the Hu-Yap65 WW domain sequence is seen as responsible for differentiation in the binding mode among the WW domains of group I.

PubMed: 11743730
DOI: 10.1006/jmbi.2000.5199

実験手法

SOLUTION NMR