Characterization of the Saccharomyces cerevisiae gene MGP1, a novel member of the ras gene superfamily that functions in the mitochondrial biogenesis

dc.contributor.advisor Alan Myers
dc.contributor.author Tzeng, Shu-Hwa
dc.contributor.department Genetics, Development and Cell Biology
dc.date 2018-08-16T15:24:04.000
dc.date.accessioned 2020-07-02T06:16:01Z
dc.date.available 2020-07-02T06:16:01Z
dc.date.copyright Wed Jan 01 00:00:00 UTC 1992
dc.date.issued 1992
dc.description.abstract <p>This dissertation characterizes Mgp1p, a mitochondrial protein that functions in mitochondrial biogenesis. Mgp1p is the first protein related to the p21[superscript] H-ras oncoprotein shown to function in mitochondria;The Saccharomyces cerevisiae gene MGP1 was isolated based on its ability to restore respiratory competence to a strain containing the nuclear petite mutation msg1-1. MGP1 codes for a protein of approximately 58 kDa, with an amino terminal sequence typical of a mitochondrial targeting peptide. A 190 residue region of Mgp1p shares approximately 30% amino acid sequence identity with any member of p21[superscript] ras-related protein superfamily, with particularly strong homology in the regions known to interact with guanine nucleotides. Multiple copies of MGP1 suppress the respiratory enzyme assembly defects caused by msg1 mutations. To demonstrate that Mgp1p is functionally similar to p21[superscript] ras-related proteins, a mutation was introduced into MGP1 that deleted the phosphate group binding region conserved in this family of guanine nucleotide binding proteins. This mutation inactivated the suppressor function of MGP1;Mgp1p co-fractionated with mitochondria in subcellular fractionation experiments. In vitro mitochondrial import experiments demonstrated Mgp1p is translocated into mitochondria by a mechanism dependent on inner membrane potential, and Mgp1p was processed during translocation. After translocation Mgp1p was bound to mitochondrial membranes. Mutation of cysteine residue 523 to a serine reduced the association of Mgp1p with mitochondrial membranes, suggesting C-terminal post-translational modifications occur for Mgp1p similar to those known for other p21[superscript] ras-related proteins. This mutation inactivated the suppressor function of MGP1;Mgp1p was produced in E. coli to facilitate biochemical analysis. Crosslinking experiments demonstrated Mgp1p expressed in E. coli is capable of binding GTP. Taken together, the data presented in this dissertation suggest Mgp1p is a p21[superscript] ras-related, GTP-binding protein attached to the mitochondrial membrane by a mechanism involving modification at its carboxyl terminus. Based on the known functions of such proteins, Mgp1p may serve as part of a signal transduction mechanism involved in communication between mitochondria and the cytosol.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/rtd/9845/
dc.identifier.articleid 10844
dc.identifier.contextkey 6366666
dc.identifier.doi https://doi.org/10.31274/rtd-180813-11201
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath rtd/9845
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/82988
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/rtd/9845/r_9223941.pdf|||Sat Jan 15 02:38:33 UTC 2022
dc.subject.disciplines Cell Biology
dc.subject.disciplines Molecular Biology
dc.subject.keywords Biochemistry and biophysics
dc.subject.keywords Molecular
dc.subject.keywords cellular
dc.subject.keywords and developmental biology
dc.title Characterization of the Saccharomyces cerevisiae gene MGP1, a novel member of the ras gene superfamily that functions in the mitochondrial biogenesis
dc.type article
dc.type.genre dissertation
dspace.entity.type Publication
relation.isOrgUnitOfPublication 9e603b30-6443-4b8e-aff5-57de4a7e4cb2
thesis.degree.level dissertation
thesis.degree.name Doctor of Philosophy
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