PDBsum entry 4z8e

Transcription

PDB id: 4z8e

Contents

Protein chains

59 a.a.

55 a.a.

Waters ×68

PDB id:

4z8e

Name:

Transcription

Title:

Tead dbd mutant -deltal1

Structure:

Transcriptional enhancer factor tef-1. Chain: a, b, c. Fragment: unp residues 28-104. Synonym: ntef-1, protein gt-iic, tea domain family member 1, tead-1, transcription factor 13, tcf-13. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tead1, tcf13, tef1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.09Å R-factor: 0.225 R-free: 0.237

Authors:

D.-S.Lee,D.C.Albarado,C.Vonrhein,C.S.Raman,S.Veeraraghavan

Key ref:

D.S.Lee et al. (2016). A Potential Structural Switch for Regulating DNA-Binding by TEAD Transcription Factors. J Mol Biol, 428, 2557-2568. PubMed id: 27016204 DOI: 10.1016/j.jmb.2016.03.008

Date:

08-Apr-15 Release date: 13-Apr-16

Protein chains

P28347  (TEAD1_HUMAN) -  Transcriptional enhancer factor TEF-1 from Homo sapiens

Seq: 426 a.a.

Struc: 59 a.a.*

Protein chain

P28347  (TEAD1_HUMAN) -  Transcriptional enhancer factor TEF-1 from Homo sapiens

Seq: 426 a.a.

Struc: 55 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B, C: E.C.?

DOI no: 10.1016/j.jmb.2016.03.008

J Mol Biol 428:2557-2568 (2016)

PubMed id: 27016204

A Potential Structural Switch for Regulating DNA-Binding by TEAD Transcription Factors.

D.S.Lee, C.Vonrhein, D.Albarado, C.S.Raman, S.Veeraraghavan.

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.