7AAH

Structure of human pERp1

7AAH の概要

• エントリーDOI: 10.2210/pdb7aah/pdb
• 分子名称: Marginal zone B- and B1-cell-specific protein, CITRIC ACID (3 entities in total)
• 機能のキーワード: folding factor, endoplasmatic reticulum, igm, immune system
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36706.90

構造登録者

Sowa, S.T.,Moilanen, A.,Biterova, E.,Saaranen, M.J.,Lehtio, L.,Ruddock, L.W. (登録日: 2020-09-04, 公開日: 2021-01-27, 最終更新日: 2024-10-16)

主引用文献

Sowa, S.T.,Moilanen, A.,Biterova, E.,Saaranen, M.J.,Lehtio, L.,Ruddock, L.W.
High-resolution Crystal Structure of Human pERp1, A Saposin-like Protein Involved in IgA, IgM and Integrin Maturation in the Endoplasmic Reticulum.
J.Mol.Biol., 433:166826-166826, 2021

PubMed 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.

PubMed: 33453188
DOI: 10.1016/j.jmb.2021.166826

実験手法

X-RAY DIFFRACTION (1.4 Å)