University of Oulu

Sven T. Sowa, Antti Moilanen, Ekaterina Biterova, Mirva J Saaranen, Lari Lehtiö, Lloyd W Ruddock, High-resolution Crystal Structure of Human pERp1, A Saposin-like Protein Involved in IgA, IgM and Integrin Maturation in the Endoplasmic Reticulum, Journal of Molecular Biology, Volume 433, Issue 5, 2021, 166826, ISSN 0022-2836, https://doi.org/10.1016/j.jmb.2021.166826

High-resolution crystal structure of human pERp1, a saposin-like protein involved in IgA, IgM and integrin maturation in the endoplasmic reticulum

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Author: Sowa, Sven T.1,2; Moilanen, Antti1; Biterova, Ekaterina1;
Organizations: 1Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 7, 90220 Oulu, Finland
2Biocenter Oulu, Aapistie 5, 90220 Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.1 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021041610685
Language: English
Published: Elsevier, 2021
Publish Date: 2021-04-16
Description:

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 Å) 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.

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Series: Journal of molecular biology
ISSN: 0022-2836
ISSN-E: 1089-8638
ISSN-L: 0022-2836
Volume: 433
Issue: 5
Article number: 166826
DOI: 10.1016/j.jmb.2021.166826
OADOI: https://oadoi.org/10.1016/j.jmb.2021.166826
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Subjects:
Funding: This work was supported by the Academy of Finland (grant numbers 266457, 272573, 287063 and 294085), Sigrid Juselius Foundation and Biocenter Oulu.
Academy of Finland Grant Number: 266457
272573
287063
294085
Detailed Information: 266457 (Academy of Finland Funding decision)
272573 (Academy of Finland Funding decision)
287063 (Academy of Finland Funding decision)
294085 (Academy of Finland Funding decision)
Copyright information: © 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  https://creativecommons.org/licenses/by-nc-nd/4.0/