Structural analysis of chaperone complex for the IgM assembly

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K06075
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Tohoku University
• Principal Investigator: Watanabe Satoshi 東北大学, 多元物質科学研究所, 助教 (50432357)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: カーゴ受容体 / クライオ電子顕微鏡 / シャペロン

Outline of Final Research Achievements

Immunoglobulin M (IgM) is secreted as a pentamer or hexamer formed by by disulfide bonds. In this study, we have investigated the structural and functional analysis of ERGIC-53, a cargo receptor involved in the biosynthesis of IgM, and determined its full-length structure by cryo-EM single-particle analysis. ERp44, a chaperone protein is also involved in the maturation of IgM monomers. We revealed the zinc-based substrate dissociation mechanism of ERp44. In addition, we have solved a cryo-EM structure of a complex between ERp44 and its client proteins, revealing molecular basis of its substrate recognition.

Free Research Field

構造生物化学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果、長年未解明であったERGIC-53の全長構造をクライオ電顕単粒子解析によって明らかにすることができた。構造解析によって血液凝固第V因子などの積荷の詳細な結合部位が明らかになり、また長いストーク領域を利用した効率的な輸送機構が明らかになった。これらの構造情報は、抗血液凝固薬の開発の基盤になることが期待できる。