ABSTRACT
M olecular chaperones and their co-chaperones o f the endoplasmic reticulum (ER) are crucial for efficient ER-associated protein biogenesis. The m ajor molecular chaperone o f the E R , BiP, is a member o f the heat shock protein 70 (H sp70) family and cooperates with co-chaperones o f the H sp40 family, as well as with nucleotide exchange factors. So far, six H sp40 co-chaperones, E R jl to ER j6 and two nucleotide exchange factors, S ill and G rp l7 0 , have been identified in mammals. In addition to the classical role o f H sp40 co-chaperones in stimulating the ATPase activity o f BiP via the characteristic J-dom ain, ERj proteins mediate various specific BiP functions based on their additional individual structural and functional properties. D uring protein transport into the E R , BiP cooperates with the two membrane-anchored ER j proteins, E R jl and E R j2/Sec63.
