2gjd
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(New page: 200px<br /><applet load="2gjd" size="450" color="white" frame="true" align="right" spinBox="true" caption="2gjd, resolution 1.75Å" /> '''Distinct functional ...)
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Revision as of 09:07, 21 November 2007
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Distinct functional domains of Ubc9 dictate cell survival and resistance to genotoxic stress
Overview
Covalent modification with SUMO alters protein function, intracellular, localization, or protein-protein interactions. Target recognition is, determined, in part, by the SUMO E2 enzyme, Ubc9, while Siz/Pias E3, ligases may facilitate select interactions by acting as substrate, adaptors. A yeast conditional Ubc9P(123)L mutant was viable at 36 degrees, C yet exhibited enhanced sensitivity to DNA damage. To define functional, domains in Ubc9 that dictate cellular responses to genotoxic stress versus, those necessary for cell viability, a 1.75-A structure of yeast Ubc9 that, demonstrated considerable conservation of backbone architecture with human, Ubc9 was solved. Nevertheless, differences in side chain geometry/charge, guided the design of human/yeast chimeras, where swapping domains, implicated in (i) binding residues within substrates that flank canonical, SUMOylation sites, (ii) interactions with the RanBP2 E3 ligase, and (iii), binding of the heterodimeric E1 and SUMO had distinct effects on cell, growth and resistance to DNA-damaging agents. Our findings establish a, functional interaction between N-terminal and substrate-binding domains of, Ubc9 and distinguish the activities of E3 ligases Siz1 and Siz2 in, regulating cellular responses to genotoxic stress.
About this Structure
2GJD is a Single protein structure of sequence from Saccharomyces cerevisiae. Active as Ubiquitin--protein ligase, with EC number 6.3.2.19 Full crystallographic information is available from OCA.
Reference
Distinct functional domains of Ubc9 dictate cell survival and resistance to genotoxic stress., van Waardenburg RC, Duda DM, Lancaster CS, Schulman BA, Bjornsti MA, Mol Cell Biol. 2006 Jul;26(13):4958-69. PMID:16782883
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