A set of endoplasmic reticulum proteins possessing properties of molecular chaperones includes Ca2+-binding proteins and members of the thioredoxin superfamily

Sanjay K. Nigam, Alfred L. Goldberg, Siew Ho, Michael F. Rohde, Kevin T. Bush, Michael Yu Sherman

Research output: Contribution to journalArticlepeer-review

255 Scopus citations

Abstract

The major proteins in the lumen of the endoplasmic reticulum (ER) are thought to function in Ca2+ sequestration or as "molecular chaperones" in the folding and assembly of membrane or secreted proteins. Based on the ability of many chaperones to bind selectively to unfolded proteins and to dissociate from them upon ATP hydrolysis, we developed an affinity chromatography method to isolate proteins with these characteristics from pancreatic or liver ER. Seven ER proteins bound selectively to denatured protein columns and were specifically eluted by ATP (10-6 M) but not by a nonhydrolyzable ATP analog. These proteins were identified with antibodies and microsequencing as the ER chaperone BiP (grp78), grp94, calreticulin, a novel 46-kDa protein that binds azido-ATP, as well as three members of the thioredoxin superfamily: protein-disulfide isomerase, ERp72, and a previously reported 50-kDa protein (p50). This set of seven proteins bound to and was eluted with ATP from a variety of denatured proteins, including histone, gelatin, α fetoprotein, thyroglobulin, lysozyme, casein, and IgG. The release of grp94, protein-disulfide isomerase, ERp72, calreticulin, and p50 was stimulated by Ca2+ in the presence of ATP. These proteins thus appear to function as Ca2+-dependent chaperones, which may account for the Ca2+ and ATP requirement for protein folding in the ER.

Original languageEnglish
Pages (from-to)1744-1749
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number3
StatePublished - 21 Jan 1994
Externally publishedYes

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