Date of Award

2010

Publication Type

Master Thesis

Degree Name

M.Sc.

Department

Chemistry and Biochemistry

Keywords

Biochemistry.

Supervisor

Vacratsis, Panayiotis (Chemistry and Biochemistry)

Rights

info:eu-repo/semantics/openAccess

Abstract

YVH1 is a highly conserved dual specificity phosphatase that possesses a novel zinc-binding domain. Although studies implicate hYVH1 in cell survival and cell cycle progression, it remains poorly characterized. In this study, association of hYVH1 with the 60S subunit was demonstrated. Oxidative stress inhibits this association, with the appearance of a 25kDa hYVH1 fragment. Domain deletion studies reveal that regions of the catalytic and zinc-binding domains facilitate ribosomal binding. Collectively, our results lead to a proposed mechanism whereby structural rearrangements in the zinc-binding domain mediate dissociation of hYVH1 from the ribosome and exposure of a proteolytic cleavage site. We have also purified several hYVH1 variants for X-ray crystallography. To date, we have obtained a low resolution solution structure of full length hYVH1 representing the first structure of any YVH1 orthologue. We anticipate that structural analysis will offer invaluable insights concerning the regulation, mode of action, and substrate specificity of hYVH1.

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