Modeling the Structure of Yeast MATα1: An HMG-Box Motif with a C-Terminal Helical Extension

Doba Jackson, Tarnisha Lawson, Robert Villafane, Lisa Gary

Department of Chemistry and Biochemistry, Huntingdon College, Montgomery, USA.
Department of Microbiology, Alabama State University, Montgomery, USA.
School of Public Health, University of Alabama Birmingham, Birmingham, USA.

DOI: 10.4236/ojbiphy.2013.31001                

Abstract

The yeast MATα1 is required for the activation of α-specific genes in Saccharomyces cerevisiae and thus confers the α-cell identity of the yeast. MATα1 contains a domain called the α-domain which has significant sequence identity to the HMG-box family of proteins. A multiple sequence alignment of several α-domains and various structurally determined HMG-box domains has revealed that both domains possess very similar structural and functional residues. We found that the basic amino acids of the N-terminal loop, the intercalating hydrophobic residues of the first helix, and the hydrophobic residues required for interactions within the core of the protein are remarkably conserved in α-domains and HMG-box proteins. Our generated molecular models suggest that the first and third helix will be shorter and that the HMG-box core is not an isolated domain. The region beyond the conserved HMG-box motif contains an extended helical region for about 20 - 30 amino acids. Structural models generated by comparative modeling and ab initio modeling reveal that this region will add two or more additional α-helices and will make significant contacts to helix III, II and I of the HMG-box core. We were able to illustrate how the extended α-domain would bind to DNA by merging of the α-domain and the LEF-1/DNA complex. The models we are reporting will be helpful in understanding how MATα1 binds to DNA with its partner MCM1 and activates transcription of α-specific genes. These models will also aid in future biophysical studies of MATα1 including the crystallization and structure determination.

Keywords

MATα1; MATα2; Gene Regulation; Mating-Type; Yeast; α-Domain; Combinatorial Control of Transcription

Conflicts of Interest

The authors declare no conflicts of interest.

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