Back to Search
Start Over
High-resolution Crystal Structure of Human pERp1, A Saposin-like Protein Involved in IgA, IgM and Integrin Maturation in the Endoplasmic Reticulum
- Source :
- Journal of molecular biology. 433(5)
- Publication Year :
- 2020
-
Abstract
- The folding of disulfide bond containing proteins in the endoplasmic reticulum (ER) is a complex process that requires protein folding factors, some of which are protein-specific. The ER resident saposin-like protein pERp1 (MZB1, CNPY5) is crucial for the correct folding of IgA, IgM and integrins. pERp1 also plays a role in ER calcium homeostasis and plasma cell mobility. As an important factor for proper IgM maturation and hence immune function, pERp1 is upregulated in many auto-immune diseases. This makes it a potential therapeutic target. pERp1 belongs to the CNPY family of ER resident saposin-like proteins. To date, five of these proteins have been identified. All are implicated in protein folding and all contain a saposin-like domain. All previously structurally characterized saposins are involved in lipid binding. However, there are no reports of CNPY family members interacting with lipids, suggesting a novel function for the saposin fold. However, the molecular mechanisms of their function remain elusive. To date, no structure of any CNPY protein has been reported. Here, we present the high-resolution (1.4 A) crystal structure of human pERp1 and confirm that it has a saposin-fold with unique structural elements not present in other saposin-fold structures. The implications for the role of CNPY proteins in protein folding in the ER are discussed.
- Subjects :
- Models, Molecular
Protein Conformation, alpha-Helical
Protein Folding
Integrin
Genetic Vectors
Gene Expression
Crystallography, X-Ray
Endoplasmic Reticulum
Saposins
Substrate Specificity
Downregulation and upregulation
Structural Biology
Escherichia coli
Humans
Protein Interaction Domains and Motifs
Amino Acid Sequence
Cloning, Molecular
Molecular Biology
Adaptor Proteins, Signal Transducing
Binding Sites
biology
Sequence Homology, Amino Acid
Chemistry
Endoplasmic reticulum
Recombinant Proteins
Cell biology
Immunity, Humoral
Immunoglobulin A
Folding (chemistry)
Immunoglobulin M
Chaperone (protein)
biology.protein
Protein folding
Calcium
Protein Conformation, beta-Strand
Antibody
Sequence Alignment
Function (biology)
Molecular Chaperones
Protein Binding
Subjects
Details
- ISSN :
- 10898638
- Volume :
- 433
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Journal of molecular biology
- Accession number :
- edsair.doi.dedup.....a54b73188bd7f435a90b34f79b10e66b