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Proc Natl Acad Sci U S A . Analysis of the structure and interactions of the SARS-CoV-2 ORF7b accessory protein

tetano

Editor, Senior Moderator
Proc Natl Acad Sci U S A


. 2024 Nov 12;121(46):e2407731121.
doi: 10.1073/pnas.2407731121. Epub 2024 Nov 7. Analysis of the structure and interactions of the SARS-CoV-2 ORF7b accessory protein

Minh-Ha Nguyen[SUP] #[/SUP][SUP] 1 [/SUP], Gyula Palfy[SUP] #[/SUP][SUP] 2 [/SUP], Marie-Laure Fogeron[SUP] 1 [/SUP], Martí Ninot Pedrosa[SUP] 1 [/SUP], Johannes Zehnder[SUP] 2 [/SUP], Vaclav Rimal[SUP] 2 [/SUP], Morgane Callon[SUP] 1 2 [/SUP], Lauriane Lecoq[SUP] 1 [/SUP], Alexander Barnes[SUP] 2 [/SUP], Beat H Meier[SUP] 2 [/SUP], Anja Böckmann[SUP] 1 [/SUP]



Affiliations
Abstract

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 α-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.

Keywords: ORF7b; SARS-CoV-2; interactions; solid-state NMR; structure.

 
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