 |
PDBsum entry 4z8e
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transcription
|
PDB id
|
|
|
|
4z8e
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
A potential structural switch for regulating DNA-Binding by tead transcription factors.
|
|
|
Authors
|
|
D.S.Lee,
C.Vonrhein,
D.Albarado,
C.S.Raman,
S.Veeraraghavan.
|
|
|
Ref.
|
|
J Mol Biol, 2016,
428,
2557-2568.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
