An extended motif in the SARS-CoV-2 spike modulates binding and release of host coatomer in retrograde trafficking

Debajit Dey; Suruchi Singh; Saif Khan; Matthew Martin; Nicholas J Schnicker; Lokesh Gakhar; Brian G Pierce; S Saif Hasan

doi:10.1038/s42003-022-03063-y

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An extended motif in the SARS-CoV-2 spike modulates binding and release of host coatomer in retrograde trafficking

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An extended motif in the SARS-CoV-2 spike modulates binding and release of host coatomer in retrograde trafficking

Debajit Dey, Suruchi Singh, Saif Khan, Matthew Martin, Nicholas J Schnicker, Lokesh Gakhar, Brian G Pierce and S Saif Hasan

Communications biology, Vol.5(1), pp.115-115

02/08/2022

DOI: 10.1038/s42003-022-03063-y

PMCID: PMC8825798

PMID: 35136165

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Abstract

β-Coronaviruses such as SARS-CoV-2 hijack coatomer protein-I (COPI) for spike protein retrograde trafficking to the progeny assembly site in endoplasmic reticulum-Golgi intermediate compartment (ERGIC). However, limited residue-level details are available into how the spike interacts with COPI. Here we identify an extended COPI binding motif in the spike that encompasses the canonical K-x-H dibasic sequence. This motif demonstrates selectivity for αCOPI subunit. Guided by an in silico analysis of dibasic motifs in the human proteome, we employ mutagenesis and binding assays to show that the spike motif terminal residues are critical modulators of complex dissociation, which is essential for spike release in ERGIC. αCOPI residues critical for spike motif binding are elucidated by mutagenesis and crystallography and found to be conserved in the zoonotic reservoirs, bats, pangolins, camels, and in humans. Collectively, our investigation on the spike motif identifies key COPI binding determinants with implications for retrograde trafficking.

Details

Title: Subtitle: An extended motif in the SARS-CoV-2 spike modulates binding and release of host coatomer in retrograde trafficking
Creators: Debajit Dey - Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA
Suruchi Singh - Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA
Saif Khan - Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, USA
Matthew Martin - University of Iowa, Pathology
Nicholas J Schnicker - Protein and Crystallography Facility, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Lokesh Gakhar - University of Iowa, Biochemistry and Molecular Biology
Brian G Pierce - Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA
S Saif Hasan - Center for Biomolecular Therapeutics, University of Maryland School of Medicine, Rockville, MD, USA. sshasan@som.umaryland.edu
Resource Type: Journal article
Publication Details: Communications biology, Vol.5(1), pp.115-115
DOI: 10.1038/s42003-022-03063-y
PMID: 35136165
PMCID: PMC8825798
NLM abbreviation: Commun Biol
eISSN: 2399-3642
Grant note: P30 GM138396 / NIGMS NIH HHS P30 CA134274 / NCI NIH HHS P30 CA086862 / NCI NIH HHS R24 GM115586 / NIGMS NIH HHS
Language: English
Date published: 02/08/2022
Academic Unit: Molecular Physiology and Biophysics; Pathology; Biochemistry and Molecular Biology
Record Identifier: 9984217230902771

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