Differential binding of Sin3 interacting repressor domains to the PAH2 domain of Sin3A

The Sin3 interacting domain (SID), originally described in the Mad family of repressors, is a novel transcriptional repressor domain that binds the PAH2 domain of corepressors Sin3A and Sin3B with high affinities. The conserved SID-like domains are reportedly present in five KLF proteins. However, the KLF SIDs and the Mad SIDs can be classified into two subtypes according to sequence similarity. Here, we report the finding from computational and experimental studies that the two subtypes of SID domains bind differentially to Sin3A. This finding offers insights into a mechanism of cell growth regulation by interactions of different subtypes of SID-containing repressor proteins with Sin3. It also provides the structural basis for developing selective modulators of Sin3. [Copyright &y& Elsevier]