Dataset Information

PERp1 is significantly up-regulated during plasma cell differentiation and contributes to the oxidative folding of immunoglobulin.

ABSTRACT: Plasma cells can synthesize and secrete thousands of Ig molecules per second, which are folded and assembled in the endoplasmic reticulum (ER) and are likely to place unusually high demands on the resident chaperones and folding enzymes. We have discovered a new resident ER protein (pERp1) that is a component of the BiP chaperone complex. PERp1 is substantially up-regulated during B to plasma cell differentiation and can be induced in B cell lines by some UPR activators, arguing that it represents a potentially new class of conditional UPR targets. In LPS-stimulated murine splenocytes, pERp1 interacted covalently via a disulfide bond with IgM monomers and noncovalently with other Ig assembly intermediates. Knockdown and overexpression experiments revealed that pERp1 promoted correct oxidative folding of Ig heavy chains and prevented off-pathway assembly intermediates. Although pERp1 has no homology with known chaperones or folding enzymes, it possesses a thioredoxin-like active site motif (CXXC), which is the signature of oxidoreductases. Mutation of this sequence did not affect its in vivo activity, suggesting that pERp1 is either a unique type of oxidoreductase or a previously unidentified class of molecular chaperone that is dedicated to enhancing the oxidative folding of Ig precursors.

SUBMITTER: Shimizu Y

PROVIDER: S-EPMC2761359 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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pERp1 is significantly up-regulated during plasma cell differentiation and contributes to the oxidative folding of immunoglobulin.

Shimizu Yuichiro Y Meunier Laurent L Hendershot Linda M LM

Proceedings of the National Academy of Sciences of the United States of America 20090917 40

Plasma cells can synthesize and secrete thousands of Ig molecules per second, which are folded and assembled in the endoplasmic reticulum (ER) and are likely to place unusually high demands on the resident chaperones and folding enzymes. We have discovered a new resident ER protein (pERp1) that is a component of the BiP chaperone complex. PERp1 is substantially up-regulated during B to plasma cell differentiation and can be induced in B cell lines by some UPR activators, arguing that it represen ...[more]

PMID: 19805157

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Dataset Information

PERp1 is significantly up-regulated during plasma cell differentiation and contributes to the oxidative folding of immunoglobulin.

Publications

pERp1 is significantly up-regulated during plasma cell differentiation and contributes to the oxidative folding of immunoglobulin.

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