Molecular Biology Commons^™

Dependence Of Endoplasmic Reticulum-Associated Degradation On The Peptide Binding Domain And Concentration Of Bip, Mehdi Kabani, Stephanie S. Kelley, Michael W. Morrow, Diana L. Montgomery, Renuka Sivendran, Mark D. Rose, Lila Gierasch, Jeffrey L. Brodsky

Lila Gierasch

ER-associated degradation (ERAD) removes defective and mis-folded proteins from the eukaryotic secretory pathway, but mutations in the ER lumenal Hsp70, BiP/Kar2p, compromise ERAD efficiency in yeast. Because attenuation of ERAD activates the UPR, we screened for kar2 mutants in which the unfolded protein response (UPR) was induced in order to better define how BiP facilitates ERAD. Among the kar2 mutants isolated we identified the ERAD-specific kar2-1 allele (Brodsky et al. J. Biol. Chem. 274, 3453–3460). The kar2-1 mutation resides in the peptide-binding domain of BiP and decreases BiP's affinity for a peptide substrate. Peptide-stimulated ATPase activity was also reduced, suggesting …