Structural Basis for Cooperative Transcription Factor Binding to the CBP Coactivator

Regulation of transcription requires interactions between transcriptional activators and transcriptional co-activator CREB binding protein (CBP). The KIX domain of CBP can bind simultaneously to two different proteins, providing an additional mechanism for transcriptional regulation. Here we describ...

Full description

Saved in:
Bibliographic Details
Published in:Journal of molecular biology 2006-02, Vol.355 (5), p.1005-1013
Main Authors: De Guzman, Roberto N., Goto, Natalie K., Dyson, H. Jane, Wright, Peter E.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
c-Myb transcription factor
CREB-Binding Protein - chemistry
CREB-Binding Protein - metabolism
Humans
KIX domain of CREB-binding protein
mixed lineage leukemia transcription factor
Models, Molecular
Molecular Sequence Data
Myeloid-Lymphoid Leukemia Protein - chemistry
Myeloid-Lymphoid Leukemia Protein - metabolism
Nuclear Magnetic Resonance, Biomolecular
Protein Binding
Protein Structure, Tertiary
Proto-Oncogene Proteins c-myb - chemistry
Proto-Oncogene Proteins c-myb - metabolism
Sequence Alignment
solution structure
ternary complex
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Regulation of transcription requires interactions between transcriptional activators and transcriptional co-activator CREB binding protein (CBP). The KIX domain of CBP can bind simultaneously to two different proteins, providing an additional mechanism for transcriptional regulation. Here we describe the solution structure of the ternary complex formed by cooperative binding of activation domains from the c-Myb and mixed lineage leukemia (MLL) transcription factors to the KIX domain. The MLL and c-Myb domains form helices that bind to two distinct hydrophobic grooves on opposite faces of KIX. Compared to the binary KIX:c-Myb complex, significant changes are observed in the structure of KIX at the MLL binding interface in the ternary complex. Two regions of KIX that are disordered in the binary complex become structured in the ternary complex: a flexible loop forms intimate contacts with bound MLL, and the C-terminal helix is extended and stabilized by MLL binding. This structural change results in the formation of additional electrostatic/polar interactions between KIX and the bound c-Myb, providing a structural basis for the cooperativity observed for the ternary complex.
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2005.09.059