Effect of translational and post-translational modifications on actin isoforms.

摘要

Actin is involved in a diverse array of eukaryotic cellular processes. In this thesis, the effects of translational and post-translational modification on the intrinsic properties of various actin isoforms are examined. Mutations in human cardiac actin implicated in the development of cardiomyopathies were studied and found to affect the rate of inorganic phosphate release from these mutant proteins. The effect of an N-terminal arginine on beta-actin was also examined and was shown to alter polymerization properties, thermal stability, inorganic phosphate release rate, and nucleotide release rates of the protein. As well, it was discovered that gamma-actin could be post-translationally modified in vitro by the small ubiquitin-related modifier (SUMO) and that this modification alters the polymerization abilities of the gamma-actin protein. The findings presented here will allow for a more comprehensive understanding of actin's role in the development of disease and the complex regulation of actin in vivo.