Extension of the binding motif of the Sin3 interacting
domain of Mad-family proteins
Sin3 forms the scaffold for a multi-protein
co-repressor complex that silences transcription via the
action of histone deacetylases. Sin3 is recruited to the
DNA by several DNA binding repressors, such as the
helix-loop-helix proteins of the Mad-family. Here, we
report a binding study, solution structure and dynamics of
the PAH2 domain of mSin3 in complex to an extended Sin3
Interacting Domain (SID) of 24 residues of Mad1, showing
that conserved residues outside the previously defined
minimal 13-residue binding motif,
viz. Met7 and
Glu23, mediate additional hydrophobic and electrostatic
interactions with PAH2. Based on these results we propose
an extended consensus sequence describing the PAH2-SID
interaction for the Mad-family, showing that residues
outside the hydrophobic core of the SID interact with PAH2
and modulate binding affinity and specificity to
appropriate levels.
PDB code 1PD7. (
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■ Ingen, H. van,
Lasonder, E., Jansen, J.F.A., Kaan, A., Spronk, C.A.E.M.,
Stunnenberg, H.G & Vuister G.W (2004) “Extension
of the binding motif of the Sin3 Interacting Domain of the
Mad-family proteins”,
Biochemistry
43, 46-53.
