Insights on the Evolutionary Conservation of Mating-Type HMG Domains are Revealed using Multiple Homology Models

Abstract

MATα1 works in coordination with MCM1 and other transcriptional regulatory proteins (ie. STE11) to activate transcription of α-specific genes and ultimately determine yeast cells mating type. Although structural knowledge exist for MCM1, MATα2 and MATa1, for MATα1 and all other mating-type homologues of MATα1, they are non-existent. Recent studies have suggested that the highly conserved alpha-domain of MATα1 belongs to the HMG family of DNA binding proteins. Analysis of 27 HMG domain structures in the Protein Data Bank allowed us to make theoretical predictions on the structure of the HMG domain of MATα1. A highly conserved α-helix required for DNA binding in all HMG domains and shares 50% homology to the structure of Lef-1/DNA. A base specific interaction using a conserved arginine is not seen in current HMG structures determined to date but is predicted in our models. Ultimately we hope that the model structures will yield further insight on the evolution of the HMG and the α-domain. Attempts to determine the structure of MATα_HMG domain by X-ray crystallography are currently being pursued and will also be discussed.