The SCAN domain mediates selective oligomerization

The SCAN domain is described as a highly conserved, leucine-rich motif of a pproximately 60 amino acids found at the amino-terminal end of zinc finger transcription factors. Although no specific biological function has been at tributed to the SCAN domain, its predicted amphipathic secondary structure led to the suggestion that this domain may mediate protein-protein associat ions. A yeast two-hybrid screen identified members of two SCAN domain prote in families that interact with the SCAN domain of the zinc finger protein Z NF202. The interacting ZNF191 protein represents the family of SCAN domain- containing zinc finger proteins, whereas the novel SDP1 protein establishes a new family of genes that encode an isolated SCAN domain. Isolated SCAN d omain proteins may form asymmetric homodimers in solution. Biochemical bind ing studies confirmed the associations of ZNF191 and SDP1 with ZNF202 and e stablished the SCAN domain as a selective hetero- and homotypic oligomeriza tion domain. SCAN mediated protein associations might therefore represent a new regulatory mechanism of transcriptional activity.