Feb 5, 2013

Analyses of the effects of all ubiquitin point mutants on yeast growth rate

Journal of Molecular Biology
Benjamin P RoscoeDaniel N A Bolon

Abstract

The amino acid sequence of a protein governs its function. We used bulk competition and focused deep sequencing to investigate the effects of all ubiquitin point mutants on yeast growth rate. Many aspects of ubiquitin function have been carefully studied, which enabled interpretation of our growth analyses in light of a rich structural, biophysical and biochemical knowledge base. In one highly sensitive cluster on the surface of ubiquitin, almost every amino acid substitution caused growth defects. In contrast, the opposite face tolerated virtually all possible substitutions. Surface locations between these two faces exhibited intermediate mutational tolerance. The sensitive face corresponds to the known interface for many binding partners. Across all surface positions, we observe a strong correlation between burial at structurally characterized interfaces and the number of amino acid substitutions compatible with robust growth. This result indicates that binding is a dominant determinant of ubiquitin function. In the solvent-inaccessible core of ubiquitin, all positions tolerated a limited number of substitutions, with hydrophobic amino acids especially interchangeable. Some mutations null for yeast growth were previously show...Continue Reading

Mentioned in this Paper

Saccharomyces cerevisiae Proteins
Proteasome Pathway
Ubiquitins
Covalent Interaction
Conjugation
Dominant-Negative Mutation
Protein Degradation, Regulatory
Molecular Helix
Galactose Measurement
Mutation, Nonsense

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