4Z8E

TEAD DBD mutant -deltaL1

Summary for 4Z8E

• Entry DOI: 10.2210/pdb4z8e/pdb
• Descriptor: Transcriptional enhancer factor TEF-1 (2 entities in total)
• Functional Keywords: transcription factor, dna binding, three helix bundle, transcription
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 24532.11

Authors

Lee, D.-S.,Albarado, D.C.,Vonrhein, C.,Raman, C.S.,Veeraraghavan, S. (deposition date: 2015-04-08, release date: 2016-04-13, Last modification date: 2024-03-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.092 Å)