Article

Heavy-chain binding protein recognizes aberrant polypeptides translocated in vitro.

Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.
Nature (impact factor: 36.28). 06/1988; 333(6168):90-3. DOI:10.1038/333090a0
Source: PubMed

ABSTRACT Immunoglobulin heavy-chain binding protein (BiP, GRP-78) associates tightly in the endoplasmic reticulum (ER) with newly synthesized proteins that are incompletely assembled, have mutant structures, or are incorrectly glycosylated. The function of BiP has been suggested to be to prevent secretion of incorrectly folded or incompletely assembled protein, to promote folding or assembly of proteins, or to solubilize protein aggregates within the ER lumen. Here we examine the interaction of BiP with newly synthesized polypeptides in an in vitro protein translation-translocation system. We find that BiP forms tight complexes with nonglycosylated yeast invertase and incorrectly disulphide-bonded prolactin, but does not associate detectably with either glycosylated invertase or correctly disulphide-bonded prolactin. Moreover, BiP associates detectably only with completed chains of prolactin, not with chains undergoing synthesis. We conclude that BiP recognizes and binds with high affinity in vitro to aberrantly folded or aberrantly glycosylated polypeptides, but not to all nascent chains as they are folding.

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Keywords

aberrantly glycosylated polypeptides
 
associate detectably
 
BiP associates detectably
 
chains undergoing synthesis
 
disulphide-bonded prolactin
 
endoplasmic reticulum
 
folding
 
glycosylated invertase
 
Immunoglobulin heavy-chain binding protein
 
incorrectly disulphide-bonded prolactin
 
incorrectly glycosylated
 
mutant structures
 
nascent chains
 
nonglycosylated yeast invertase
 
proteins
 
synthesized polypeptides
 
synthesized proteins
 
vitro protein translation-translocation system
 

C K Kassenbrock