Structural diversity in p160/CREB-binding protein coactivator complexes.
Ligand-induced transcription by nuclear receptors involves the recruitment of p160 coactivators such as steroid receptor coactivator 1 (SRC1), in complex with histone acetyltransferases such as CREB-binding protein (CBP) and p300. Here we describe the solution structure of a complex formed by the SRC1 interaction domain (SID) of CBP and the activation domain (AD1) of SRC1, both of which contain four helical regions (Calpha1, Calpha2, Calpha3, and Calpha3' in CBP and Salpha1, Salpha2', Salpha2, and Salpha3 in SRC1). A tight four-helix bundle is formed between Salpha1, Calpha1, Calpha2, and Calpha3 that is capped by Salpha3. In contrast to the structure of the AD1 domain of the related p160 protein ACTR in complex with CBP SID, the sequences forming Salpha2' and Salpha2 in SRC1 AD1 are not involved in the interface between the two domains but rather serve to position Salpha3. Thus, although the CBP SID domain adopts a similar fold in complex with different p160 proteins, the topologies of the AD1 domains are strikingly different, a feature that is likely to contribute to functional specificity of these coactivator complexes.
Department of Biochemistry, Henry Wellcome Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, United Kingdom.
Lorna
L
Waters
Baigong
B
Yue
Vaclav
V
Veverka
Philip
P
Renshaw
Janice
J
Bramham
Sachiko
S
Matsuda
Thomas
T
Frenkiel
Geoffrey
G
Kelly
Frederick
F
Muskett
Mark
M
Carr
David M
DM
Heery
D000595:Amino Acid Sequence; D000818:Animals; D050882:CREB-Binding Protein / Q000737:chemistry*; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry; D056920:Nuclear Receptor Coactivator 1; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry
D004268:DNA-Binding Proteins; C491719:MYBBP1A protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D050882:CREB-Binding Protein; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; C538861:Ncoa1 protein, mouse; D056920:Nuclear Receptor Coactivator 1