5EMV

Crystal structure of the palmitoylated human TEAD2 transcription factor

5EMV の概要

• エントリーDOI: 10.2210/pdb5emv/pdb
• 関連するPDBエントリー: 5EMW
• 分子名称: Transcriptional enhancer factor TEF-4 (2 entities in total)
• 機能のキーワード: palmitoylated protein, transcription
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus: Q15562
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53883.09

構造登録者

Noland, C.L.,Gierke, S.,Schnier, P.D.,Murray, J.,Sandoval, W.N.,Sagolla, M.,Dey, A.,Hannoush, R.N.,Fairbrother, W.J.,Cunningham, C.N. (登録日: 2015-11-06, 公開日: 2015-12-23, 最終更新日: 2023-09-27)

主引用文献

Noland, C.L.,Gierke, S.,Schnier, P.D.,Murray, J.,Sandoval, W.N.,Sagolla, M.,Dey, A.,Hannoush, R.N.,Fairbrother, W.J.,Cunningham, C.N.
Palmitoylation of TEAD Transcription Factors Is Required for Their Stability and Function in Hippo Pathway Signaling.
Structure, 24:179-186, 2016

PubMed Abstract: The Hippo signaling pathway is responsible for regulating the function of TEAD family transcription factors in metazoans. TEADs, with their co-activators YAP/TAZ, are critical for controlling cell differentiation and organ size through their transcriptional activation of genes involved in cell growth and proliferation. Dysregulation of the Hippo pathway has been implicated in multiple forms of cancer. Here, we identify a novel form of regulation of TEAD family proteins. We show that human TEADs are palmitoylated at a universally conserved cysteine, and report the crystal structures of the human TEAD2 and TEAD3 YAP-binding domains in their palmitoylated forms. These structures show a palmitate bound within a highly conserved hydrophobic cavity at each protein's core. Our findings also demonstrate that this modification is required for proper TEAD folding and stability, indicating a potential new avenue for pharmacologically regulating the Hippo pathway through the modulation of TEAD palmitoylation.

PubMed: 26724994
DOI: 10.1016/j.str.2015.11.005

実験手法

X-RAY DIFFRACTION (2 Å)