Which protein facilitates ER protein folding by recognizing exposed hydrophobic regions?
Early folding intermediates expose hydrophobic clusters that normally bury within native core and are highly aggregation-prone in crowded ER environment at high protein concentration. Recognition of such patches is specialized function of Hsp70 family member BiP, also called GRP78 encoded by HSPA5 gene, abundant in ER lumen. Its C-terminal substrate binding domain forms beta-sandwich hydrophobic cleft with lid that binds extended stretches five to seven residues enriched in leucine, isoleucine, valine, phenylalanine and tryptophan via van der Waals contacts. ATP-bound open conformation has low
Ref: Mayer & Bukau, Cell Mol Life Sci 62: 2005, BiP Binding Hydrophobic Patches.
