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 a-helices of
PAH2 form a hydrophobic cleft that accommodates an
amphipathic Mad1 a-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.
PDB code 1E91. (
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■ Spronk, C.A.E.M., Tessari, M., Kaan, A.M., Jansen,
J.F.A., Vermeulen, M., Stunnenberg, H.G & Vuister, G.W.
(2000) "The Mad1-Sin3B interaction involves a novel helical
fold",
Nature Struct. Biol. 7,
1100-1104.
■ Spronk, C.A.E.M., Jansen, J.F.A., Tessari, M.,
Kaan, A.M., Aelen, J.M.A., Lasonder, E., M., Stunnenberg,
H.G & Vuister, G.W (2001) "Sequence-specific assignment
of the PAH2 domain of Sin3B free- and bound to Mad1",
J. Biomol. NMR 19, 377-378.
