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

DOI: 10.1016/j.jmb.2021.166826 DOI Help

Authors: Sven T. Sowa (University of Oulu) , Antti Moilanen (University of Oulu) , Ekaterina Biterova (University of Oulu) , Mirva J. Saaranen (University of Oulu) , Lari Lehtio (University of Oulu) , Lloyd W. Ruddock (University of Oulu)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Molecular Biology

State: Published (Approved)
Published: January 2021

Open Access Open Access

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.

Journal Keywords: protein folding; CNPY family; chaperone; MZB1; immunoglobulin

Subject Areas: Biology and Bio-materials

Instruments: I24-Microfocus Macromolecular Crystallography

Added On: 27/01/2021 09:03


Discipline Tags:

Autoimmune Diseases Health & Wellbeing Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)