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Structural insight into the dimerization of human protein disulfide isomerase.

ABSTRACT: Protein disulfide isomerases (PDIs) are responsible for catalyzing the proper oxidation and isomerization of disulfide bonds of newly synthesized proteins in the endoplasmic reticulum (ER). Here, it is shown that human PDI (PDIA1) dimerizes in vivo and proposed that the dimerization of PDI has physiological relevance by autoregulating its activity. The crystal structure of the dimeric form of noncatalytic bb' domains of human PDIA1 determined to 2.3 Å resolution revealed that the formation of dimers occludes the substrate binding site and may function as a mechanism to regulate PDI activity in the ER.

SUBMITTER: Bastos-Aristizabal S

PROVIDER: S-EPMC4005713 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Structural insight into the dimerization of human protein disulfide isomerase.

Bastos-Aristizabal Sara S Kozlov Guennadi G Gehring Kalle K

Protein science : a publication of the Protein Society 20140311 5

Protein disulfide isomerases (PDIs) are responsible for catalyzing the proper oxidation and isomerization of disulfide bonds of newly synthesized proteins in the endoplasmic reticulum (ER). Here, it is shown that human PDI (PDIA1) dimerizes in vivo and proposed that the dimerization of PDI has physiological relevance by autoregulating its activity. The crystal structure of the dimeric form of noncatalytic bb' domains of human PDIA1 determined to 2.3 Å resolution revealed that the formation of di ...[more]

PMID: 24549644

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2021-02-20 | GSE167097 | GEO

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Role of dimerization in the catalytic properties of the Escherichia coli disulfide isomerase DsbC.

Project description:The bacterial protein-disulfide isomerase DsbC is a homodimeric V-shaped enzyme that consists of a dimerization domain, two alpha-helical linkers, and two opposing thioredoxin fold catalytic domains. The functional significance of the two catalytic domains of DsbC is not well understood yet. We have engineered heterodimer-like DsbC derivatives covalently linked via (Gly(3)-Ser) flexible linkers. We either inactivated one of the catalytic sites (CGYC), or entirely removed one of the catalytic domains while maintaining the putative binding area intact. Variants having a single active catalytic site display significant levels of isomerase activity. Furthermore, mDsbC[H45D]-dim[D53H], a DsbC variant lacking an entire catalytic domain but with an intact dimerization domain, also showed isomerase activity, albeit at lower levels. In addition, the absence of the catalytic domain allowed this protein to catalyze in vivo oxidation. Our results reveal that two catalytic domains in DsbC are not essential for disulfide bond isomerization and that a determining feature in isomerization is the availability of a substrate binding domain.

| S-EPMC2781991 | biostudies-literature

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