2L4J

Yap ww2

2L4J の概要

• エントリーDOI: 10.2210/pdb2l4j/pdb
• NMR情報: BMRB: 17241
• 分子名称: Yes-associated protein 2 (YAP2) (1 entity in total)
• 機能のキーワード: ww domain, yap, medaka, transcription
• 由来する生物種: Oryzias latipes (bony fishes, medaka)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 5130.57

構造登録者

Webb, C.,Upadhyay, A.,Furutani-Seiki, M.,Bagby, S. (登録日: 2010-10-07, 公開日: 2010-11-03, 最終更新日: 2024-05-01)

主引用文献

Webb, C.,Upadhyay, A.,Giuntini, F.,Eggleston, I.,Furutani-Seiki, M.,Ishima, R.,Bagby, S.
Structural Features and Ligand Binding Properties of Tandem WW Domains from YAP and TAZ, Nuclear Effectors of the Hippo Pathway.
Biochemistry, 50:3300-3309, 2011

PubMed Abstract: The paralogous multifunctional adaptor proteins YAP and TAZ are the nuclear effectors of the Hippo pathway, a central mechanism of organ size control and stem cell self-renewal. WW domains, mediators of protein-protein interactions, are essential for YAP and TAZ function, enabling interactions with PPxY motifs of numerous partner proteins. YAP has single and double WW domain isoforms (YAP1 and YAP2) whereas only a single WW domain isoform of TAZ has been described to date. Here we identify the first example of a double WW domain isoform of TAZ. Using NMR, we have characterized conformational features and peptide binding of YAP and TAZ tandem WW domains (WW1-WW2). The solution structure of YAP WW2 confirms that it has a canonical three-stranded antiparallel β-sheet WW domain fold. While chemical shift-based analysis indicates that the WW domains in the tandem WW pairs retain the characteristic WW domain fold, 15N relaxation data show that, within the respective WW pairs, YAP WW1 and both WW1 and WW2 of TAZ undergo conformational exchange. 15N relaxation data also indicate that the linker between the WW domains is flexible in both YAP and TAZ. Within both YAP and TAZ tandem WW pairs, WW1 and WW2 bind single PPxY-containing peptide ligand concurrently and noncooperatively with sub-mM affinity. YAP and TAZ WW1-WW2 bind a dual PPxY-containing peptide with approximately 6-fold higher affinity. Our results indicate that both WW domains in YAP and TAZ are functional and capable of enhanced affinity binding to multi-PPxY partner proteins such as LATS1, ErbB4, and AMOT.

PubMed: 21417403
DOI: 10.1021/bi2001888

実験手法

SOLUTION NMR