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

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

doi:10.1038/s42003-022-03063-y

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

Journal Article · 08 February 2022 · Communications Biology

DOI: https://doi.org/10.1038/s42003-022-03063-y · OSTI ID:1847128

^[1]; Singh, Suruchi ^[1];

^[2]; Martin, Matthew ^[3];

^[4]; Gakhar, Lokesh ^[5];

^[6];

^[7]

Univ. of Maryland School of Medicine, Baltimore, MD (United States)
Univ. of Iowa, Iowa City, IA (United States). Carver College of Medicine; Univ. of Southern California, Los Angeles, CA (United States)
Univ. of Maryland School of Medicine, Baltimore, MD (United States); Univ. of Pittsburgh, PA (United States)
Univ. of Iowa, Iowa City, IA (United States). Carver College of Medicine
Univ. of Iowa, Iowa City, IA (United States). Carver College of Medicine; PAQ Therapeutics, Cambridge, MA (United States)
Univ. of Maryland, College Park, MD (United States)
Univ. of Maryland School of Medicine and Medical Center, Baltimore and Rockville, MD (United States)

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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Cancer Institute; National Institute of General Medical Sciences (NIGMS); USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357; SC0012704

OSTI ID:: 1847128

Journal Information:: Communications Biology, Journal Name: Communications Biology Journal Issue: 1 Vol. 5; ISSN 2399-3642

Publisher:: Springer NatureCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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59 BASIC BIOLOGICAL SCIENCES
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biophysical methods
protein structure predictions
x-ray crystallography

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

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