Analysis of the structure and interactions of the SARS-CoV-2 ORF7b accessory protein

• 成果类型: Article
• 署名作者: Ha Nguyen, Minh-; Palfy, Gyula; Fogeron, Marie-Laure; Pedrosa, Marti Ninot; Zehnder, Johannes; Rimal, Vaclav; Callon, Morgane; Lecoq, Lauriane; Barnes, Alexander; Meier, Beat H.; Bockmann, Anja
• 署名单位: Universite Claude Bernard Lyon 1; Centre National de la Recherche Scientifique (CNRS)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10865
• DOI: 10.1073/pnas.2407731121
• 发表日期: 2024-11-12
• 关键词: chemical-shift index; secondary structure; transmembrane domain; nmr-spectroscopy; sars-cov; assignment; identification; phospholamban

摘要

SARS-CoV-2 carries a sizeable number of proteins that are accessory to replication but may be essential for virus-host interactions and modulation of the host immune response. Here, we investigated the structure and interactions of the largely unknown ORF7b, a small membranous accessory membrane protein of SARS- CoV-2. We show that structural predictions indicate a transmembrane (TM) leucine zipper for ORF7b, and experimentally confirm the predominantly alpha- helical secondary structure within a phospholipid membrane mimetic by solid- state NMR. We also show that ORF7b forms heterogeneous higher- order multimers. We determined ORF7b interactions with cellular TM leucine zipper proteins using both biochemical and NMR approaches, providing evidence for ORF7b interaction with the TM domains of E- cadherin, as well as phospholamban. Our results place ORF7b as a hypothetical interferer in cellular processes that utilize leucine zipper motifs in transmembrane multimerization domains.