A lysine-rich region within fungal BAG domain-containing proteins mediates a novel association with ribosomes.
Heat shock protein 70 (Hsp70) is a highly conserved molecular chaperone that assists in the folding of nascent chains and the repair of unfolded proteins through iterative cycles of ATP binding, hydrolysis, and nucleotide exchange tightly coupled to polypeptide binding and release. Cochaperones, including nucleotide exchange factors (NEFs), modulate the rate of ADP/ATP exchange and serve to recruit Hsp70 to distinct processes or locations. Among three nonrelated 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 a 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 NEFs serves a previously unknown role in fungal protein biogenesis based on the coincident recruitment of ribosomes and Hsp70 to the ER membrane.
Department of Microbiology and Molecular Genetics, University of Texas Medical School, Houston, Texas, USA.
Jacob
J
Verghese
Kevin A
KA
Morano
D002176:Candida albicans / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D017353:Gene Deletion; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D008239:Lysine / Q000032:analysis; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D054683:Ribosome Subunits, Large, Eukaryotic / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; C111099:SNL1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D008239:Lysine