THE HOMEODOMAIN - A NEW FACE FOR THE HELIX-TURN-HELIX

The discovery of conserved protein domains found in many Drosophila an d mammalian developmental gene products suggests that fundamental deve lopmental processes are conserved throughout evolution. Our understand ing of development has been enhanced by the discovery of the widesprea d role of the homeodomain (HD). The action of HD-containing proteins a s transcriptional regulators is mediated through a helix-turn-helix mo tif which confers sequence specific DNA binding. Unexpectedly, the wel l conserved structural homology between the HD and the prokaryotic hel ix-turn-helix proteins contrasts with their divergent types of physica l interaction with DNA. A C-terminal extension of the HD recognition h elix has assumed the role that the N-terminus of the prokaryotic helix plays for specification of DNA binding preference. However, the HD ap pears also capable of recognizing DNA in an alternative way and its sp ecificity in vivo may be modified by regions outside the helix-turn-he lix motif. We propose that this intrinsic complexity of the HD, as wel l as its frequent association with other DNA binding domains, explains the functional specificity achieved by genes encoding highly related HDs.