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

Journal Article · · Communications Biology
 [1];  [1];  [2];  [3];  [4];  [5];  [6];  [7]
  1. Univ. of Maryland School of Medicine, Baltimore, MD (United States)
  2. Univ. of Iowa, Iowa City, IA (United States). Carver College of Medicine; Univ. of Southern California, Los Angeles, CA (United States)
  3. Univ. of Maryland School of Medicine, Baltimore, MD (United States); Univ. of Pittsburgh, PA (United States)
  4. Univ. of Iowa, Iowa City, IA (United States). Carver College of Medicine
  5. Univ. of Iowa, Iowa City, IA (United States). Carver College of Medicine; PAQ Therapeutics, Cambridge, MA (United States)
  6. Univ. of Maryland, College Park, MD (United States)
  7. Univ. of Maryland School of Medicine and Medical Center, Baltimore and Rockville, MD (United States)
+ Show Author Affiliations
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.
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
Alternate ID(s):
OSTI ID: 1855485
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

References (62)

A weak COPI binding motif in the cytoplasmic tail of SARS‐CoV‐2 spike glycoprotein is necessary for its cleavage, glycosylation, and localization journal May 2021
beta′-COP, a novel subunit of coatomer. journal July 1993
A 102 kDa subunit of a Golgi-associated particle has homology to beta subunits of trimeric G proteins. journal July 1993
Relaxation of backbone bond geometry improves protein energy landscape modeling: Relaxation of Backbone Bond Geometry journal November 2013
MolProbity: More and better reference data for improved all-atom structure validation: PROTEIN SCIENCE.ORG journal November 2017
Protein Structure Modeling with MODELLER book January 2014
Copa Syndrome: a Novel Autosomal Dominant Immune Dysregulatory Disease journal April 2016
Purification of a novel class of coated vesicles mediating biosynthetic protein transport through the Golgi stack journal July 1989
β-COP, a 110 kd protein associated with non-clathrin-coated vesicles and the golgi complex, shows homology to β-adaptin journal February 1991
Coatomer is essential for retrieval of dilysine-tagged proteins to the endoplasmic reticulum journal December 1994
Camels, MERS-CoV, and other emerging infections in east Africa journal January 2016
Ecology, evolution and classification of bat coronaviruses in the aftermath of SARS journal January 2014
SARS-CoV and emergent coronaviruses: viral determinants of interspecies transmission journal December 2011
Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak journal April 2020
Molecular Basis for Recognition of Dilysine Trafficking Motifs by COPI journal December 2012
A coat subunit of Golgi-derived non-clathrin-coated vesicles with homology to the clathrin-coated vesicle coat protein β-adaptin journal January 1991
'Coatomer': a cytosolic protein complex containing subunits of non-clathrin-coated Golgi transport vesicles journal January 1991
Rules for the recognition of dilysine retrieval motifs by coatomer journal March 2013
Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor journal October 2013
COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis journal April 2015
SARS — beginning to understand a new virus journal December 2003
Architecture of the SARS coronavirus prefusion spike journal July 2006
Origin and cross-species transmission of bat coronaviruses in China journal August 2020
Sequences in the cytoplasmic tail of SARS-CoV-2 Spike facilitate expression at the cell surface and syncytia formation journal September 2021
Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins journal May 2020
Isolation of a Novel Coronavirus from a Man with Pneumonia in Saudi Arabia journal November 2012
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine journal December 2020
Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats journal September 2005
A simple physical model for binding energy hot spots in protein-protein complexes journal October 2002
Retrieval of transmembrane proteins to the endoplasmic reticulum. journal April 1993
En bloc incorporation of coatomer subunits during the assembly of COP- coated vesicles [published erratum appears in J Cell Biol 1994 Jul;126(2):589] journal March 1994
Signal-mediated retrieval of a membrane protein from the Golgi to the ER in yeast. journal November 1994
The α- and β′-COP WD40 Domains Mediate Cargo-selective Interactions with Distinct Di-lysine Motifs journal March 2004
ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules journal May 2016
New Algorithms and Methods to Estimate Maximum-Likelihood Phylogenies: Assessing the Performance of PhyML 3.0 journal March 2010
Evidence for zoonotic origins of Middle East respiratory syndrome coronavirus journal February 2016
Phaser crystallographic software journal July 2007
The detection of sub-units within the crystallographic asymmetric unit journal January 1962
Coot model-building tools for molecular graphics journal November 2004
HKL -3000: the integration of data reduction and structure solution – from diffraction images to an initial model in minutes journal July 2006
XDS journal January 2010
Towards automated crystallographic structure refinement with phenix.refine journal March 2012
How good are my data and what is the resolution? journal June 2013
Isolation and Characterization of Viruses Related to the SARS Coronavirus from Animals in Southern China journal October 2003
Bats Are Natural Reservoirs of SARS-Like Coronaviruses journal October 2005
Bimodal Interaction of Coatomer with the p24 Family of Putative Cargo Receptors journal September 1996
Coatomer Interaction with Di-Lysine Endoplasmic Reticulum Retention Motifs journal March 1994
A structure of the COPI coat and the role of coat proteins in membrane vesicle assembly journal July 2015
A subcellular map of the human proteome journal May 2017
Prevalence and Genetic Diversity of Coronaviruses in Bats from China journal July 2006
The Cytoplasmic Tail of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Contains a Novel Endoplasmic Reticulum Retrieval Signal That Binds COPI and Promotes Interaction with Membrane Protein journal March 2007
Discovery of Seven Novel Mammalian and Avian Coronaviruses in the Genus Deltacoronavirus Supports Bat Coronaviruses as the Gene Source of Alphacoronavirus and Betacoronavirus and Avian Coronaviruses as the Gene Source of Gammacoronavirus and Deltacoronavirus journal January 2012
Intracellular Targeting Signals Contribute to Localization of Coronavirus Spike Proteins near the Virus Assembly Site journal June 2004
Synthesis and Characterization of a Native, Oligomeric Form of Recombinant Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein journal October 2004
Structure and orientation of expressed bovine coronavirus hemagglutinin-esterase protein journal April 1990
Coronavirus M proteins accumulate in the Golgi complex beyond the site of virion budding journal October 1994
Protein interactions during coronavirus assembly journal December 1997
The predictors of 3- and 30-day mortality in 660 MERS-CoV patients journal September 2017
Alpha-COP can discriminate between distinct, functional di-lysine signals in vitro and regulates access into retrograde transport journal December 1998
Computational Design of the Affinity and Specificity of a Therapeutic T Cell Receptor journal February 2014
Isolation of MERS Coronavirus from a Dromedary Camel, Qatar, 2014 journal August 2014
Collaboration gets the most out of software journal September 2013

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
SARS-CoV-2
biophysical methods
protein structure predictions
x-ray crystallography