The Mad1-Sin3B interaction involves a novel helical fold.
Sin3A or Sin3B are components of a corepressor complex that mediates repression by transcription factors such as the helix-loop-helix proteins Mad and Mxi. Members of the Mad/Mxi family of repressors play important roles in the transition between proliferation and differentiation by down-regulating the expression of genes that are activated by the proto-oncogene product Myc. Here, we report the solution structure of the second paired amphipathic helix (PAH) domain (PAH2) of Sin3B in complex with a peptide comprising the N-terminal region of Mad1. This complex exhibits a novel interaction fold for which we propose the name 'wedged helical bundle'. Four alpha-helices of PAH2 form a hydrophobic cleft that accommodates an amphipathic Mad1 alpha-helix. Our data further show that, upon binding Mad1, secondary structure elements of PAH2 are stabilized. The PAH2-Mad1 structure provides the basis for determining the principles of protein interaction and selectivity involving PAH domains.
Spronk
C A
CA
Department of Biophysical Chemistry, NSR Center, University of Nijmegen, The Netherlands.
Tessari
M
M
Kaan
A M
AM
Jansen
J F
JF
Vermeulen
M
M
Stunnenberg
H G
HG
Vuister
G W
GW
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D017124:Conserved Sequence; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D012996:Solutions; D013379:Substrate Specificity; D014157:Transcription Factors
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C501384:MAD1L1 protein, human; C000715470:MAS1 protein, human; C501385:Mad1l1 protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000090063:Proto-Oncogene Mas; D012097:Repressor Proteins; C492042:SIN3B protein, human; C115812:Sin3b protein, mouse; D012996:Solutions; D014157:Transcription Factors