OJBIPHY  Vol.3 No.1 , January 2013
Modeling the Structure of Yeast MATα1: An HMG-Box Motif with a C-Terminal Helical Extension
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.
Cite this paper: D. Jackson, T. Lawson, R. Villafane and L. Gary, "Modeling the Structure of Yeast MATα1: An HMG-Box Motif with a C-Terminal Helical Extension," Open Journal of Biophysics, Vol. 3 No. 1, 2013, pp. 1-12. doi: 10.4236/ojbiphy.2013.31001.

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