Originally published as Genetics Published Articles Ahead of Print on July 5, 2005.

Genetics, Vol. 171, 469-476, October 2005, Copyright © 2005
doi:10.1534/genetics.105.045237

Mutational Hypersensitivity of a Gene Regulatory Protein: Saccharomyces cerevisiae Gal80p

Karsten Melcher1

Institute of Microbiology, Biocenter Niederursel, Goethe University, 60439 Frankfurt, Germany and School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, United Kingdom

1 Address for correspondence: School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, United Kingdom.
E-mail: k.melcher{at}ulster.ac.uk

The inhibitor of galactose catabolic (GAL) gene expression in Saccharomyces cerevisiae, Gal80p, interacts with the activator Gal4p and the signal transducer Gal3p and self-associates. Selection for loss of Gal80p inhibitor function yielded gal80 mutants at an extremely high rate. Out of these, 21 nonoverlapping point mutants were identified; each were due to a single-amino-acid exchange in conserved residues. Semiquantitative biochemical analysis of the corresponding mutant proteins revealed that each of the 21 amino acid alterations caused simultaneous defects in every single protein-protein interaction and in Gal80's structural integrity. Thus, Gal80 provides an unprecedented example for a protein's structural sensitivity to minimal sequence alterations.




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