4Z8E

TEAD DBD mutant -deltaL1

4Z8E の概要

• エントリーDOI: 10.2210/pdb4z8e/pdb
• 分子名称: Transcriptional enhancer factor TEF-1 (2 entities in total)
• 機能のキーワード: transcription factor, dna binding, three helix bundle, transcription
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 24532.11

構造登録者

Lee, D.-S.,Albarado, D.C.,Vonrhein, C.,Raman, C.S.,Veeraraghavan, S. (登録日: 2015-04-08, 公開日: 2016-04-13, 最終更新日: 2024-03-06)

主引用文献

Lee, D.S.,Vonrhein, C.,Albarado, D.,Raman, C.S.,Veeraraghavan, S.
A Potential Structural Switch for Regulating DNA-Binding by TEAD Transcription Factors.
J.Mol.Biol., 428:2557-2568, 2016

PubMed Abstract: TEA domain (TEAD) transcription factors are essential for the normal development of eukaryotes and are the downstream effectors of the Hippo tumor suppressor pathway. Whereas our earlier work established the three-dimensional structure of the highly conserved DNA-binding domain using solution NMR spectroscopy, the structural basis for regulating the DNA-binding activity remains unknown. Here, we present the X-ray crystallographic structure and activity of a TEAD mutant containing a truncated L1 loop, ΔL1 TEAD DBD. Unexpectedly, the three-dimensional structure of the ΔL1 TEAD DBD reveals a helix-swapped homodimer wherein helix 1 is swapped between monomers. Furthermore, each three-helix bundle in the domain-swapped dimer is a structural homolog of MYB-like domains. Our investigations of the DNA-binding activity reveal that although the formation of the three-helix bundle by the ΔL1 TEAD DBD is sufficient for binding to an isolated M-CAT-like DNA element, multimeric forms are deficient for cooperative binding to tandemly duplicated elements, indicating that the L1 loop contributes to the DNA-binding activity of TEAD. These results suggest that switching between monomeric and domain-swapped forms may regulate DNA selectivity of TEAD proteins.

PubMed: 27016204
DOI: 10.1016/j.jmb.2016.03.008

実験手法

X-RAY DIFFRACTION (2.092 Å)