Medina B, Paraskevopoulos K, Boehringer J, Sznajder A, Robertson M, Endicott J, Gordon C

The ubiquitin proteasome system (UPS) is essential for maintaining a functional cell. Not only does it remove incorrectly folded proteins, it also regulates protein levels to ensure their appropriate spatial and temporal distribution. Proteins marked for degradation by the addition of K48-linked ubiquitin (Ub) chains are recognised by shuttle factors ...

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and transported to the 26S proteasome. One of these shuttle factors, Schizosaccharomyces pombe Rhp23, has an unusual domain architecture. It comprises an N-terminal ubiquitin like (UBL) domain that can recognise the proteasome followed by two ubiquitin associated (UBA) domains, termed UBA1 and UBA2, which can bind Ub. This architecture is conserved up to humans suggesting that both domains are important for Rhp23 function. Such an extent of conservation raises the question as to why, in contrast to all other shuttle proteins, does Rhp23 require two UBA domains? We have performed in vitro Ub binding assays using domain swap chimeric proteins and mutated domains in isolation as well as in the context of the full-length protein to reveal that the Ub- binding properties of the UBA domains are context dependent. In vivo the internal Rhp23 UBA1 domain provides sufficient Ub recognition for the protein to function without UBA2.

Date: Oct. 04, 2012

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