The Mad1-Sin3B interaction involves a novel helical fold

Sin3A or Sin3B are components of a corepressor complex that mediates repres sion 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 t he transition between proliferation and differentiation by down-regulating the expression of genes that are activated by the proto-oncogene product My c. 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 o f 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 basi s for determining the principles of protein interaction and selectivity inv olving PAH domains.