ABSTRACT
Protein transport into the endoplasmic reticulum (ER) involves a protein translocase that resides in the E R membrane and is highly conserved between lower and higher eukaryotes. The Sec61 complex forms the central com ponent o f this translocase, providing a path for the newly synthesized polypeptide on its way into the membrane or the lumen o f the E R . The membrane proteins Sec62 and Sec63, plus the molecular chaperone BiP, are additional subunits o f the protein translocase and couple translocation to the hydrolysis o f ATP. In humans, ERj 1 appears to provide a functional alternative to the Sec62/Sec63 complex. Furthermore, S ill and G rp 170 are alternatively acting nucleotide exchange factors for BiP. The essential character o f BiP was emphasized by the recent discovery that inactivation o f human BiP by a bacterial cytotoxin causes life-threatening complications, such as haemolytic uraemic syndrome. O n the other hand, genetic work has identified m utations in the human SEC63 gene as one cause o f autosomal dom inant polycystic liver disease and mutations in the human SIL1 gene as one cause for a neurodegenerative disorder. Thus, redundant components o f the protein translocation machinery o f the E R are targets o f genomic alterations that can cause nonlethal human diseases.
