Verghese J, Morano KA

Heat shock protein (Hsp) 70 is a highly conserved molecular chaperone that assists in the folding of nascent chains and repair of unfolded proteins through iterative cycles of ATP binding, hydrolysis and nucleotide exchange tightly coupled to polypeptide binding and release. Co-chaperones, including nucleotide exchange factors (NEFs), modulate the rate ...

Read More

of ADP/ATP exchange and serve to recruit Hsp70 to distinct processes or locations. Among three non-related cytosolic NEFs in Saccharomyces cerevisiae, the Bag-1 homolog SNL1 is unique in being tethered to the endoplasmic reticulum (ER) membrane. We demonstrate here a novel physical association between Snl1 and the intact ribosome. This interaction is both independent of and concurrent with binding to Hsp70 and is not dependent on membrane localization. The ribosome binding site is identified as a short lysine-rich motif within the amino terminus of the Snl1 BAG domain distinct from the Hsp70 interaction region. Additionally, we demonstrate ribosome association with the Candida albicans Snl1 homolog and localize this putative NEF to a perinuclear/ER membrane, suggesting functional conservation in fungal BAG domain-containing proteins. We therefore propose that the Snl1 family of NEF serves a previously unknown role in fungal protein biogenesis based on coincident recruitment of ribosomes and Hsp70 to the ER membrane.

Date: May. 25, 2012

View in: Pubmed Google Scholar

131731