Evidence map›Paper›PMID 36824920›Full record

ArticleResearch square2023

Integrated analyses reveal a hinge glycan regulates coronavirus spike tilting and virus infectivity.

David Chmielewski, Eric A Wilson, Grigore Pintilie, Peng Zhao, Muyuan Chen, Michael F Schmid, Graham Simmons, Lance Wells, Jing Jin, Abhishek Singharoy and 1 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in Research square, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 1 country.

David ChmielewskiBiophysics Graduate Program, Stanford University, Stanford, CA 94305, USA.
Eric A WilsonSchool of Molecular Sciences, Biodesign Institute, Arizona State University, Tempe, AZ USA.ORCID 0000-0002-4104-1445
Grigore PintilieDepartment of Bioengineering, and of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
Peng ZhaoComplex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.ORCID 0000-0002-9296-5293
Muyuan ChenDivision of CryoEM and Bioimaging, SSRL, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA 94025, USA.
Michael F SchmidDivision of CryoEM and Bioimaging, SSRL, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA 94025, USA.ORCID 0000-0003-1077-5750
Graham SimmonsVitalant Research Institute, San Francisco, CA, 94118, USA.
Lance WellsComplex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.ORCID 0000-0003-4956-5363
Jing JinDepartment of Bioengineering, and of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
Abhishek SingharoySchool of Molecular Sciences, Biodesign Institute, Arizona State University, Tempe, AZ USA.ORCID 0000-0002-9000-2397
Wah ChiuBiophysics Graduate Program, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-8910-3078
SLAC National Accelerator Laboratory · USArizona State University · USStanford University · USUniversity of California, San Francisco · USUniversity of Georgia · US

Funding

Molecular Interactions of HIV-1 with the Nuclear Pore ComplexR01AI148382 · NIAID · EMORY UNIVERSITY · PI MELIKIAN, GREGORY B, SARAFIANOS, STEFAN G · 2019 to 2022
$5.5M
SUPPORT AND DEVELOPMENT OF EMAN FOR ELECTRON MICROSCOPY IMAGE PROCESSINGR01GM080139 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI LUDTKE, STEVEN J · 2006 to 2022
$5.4M
Origin of N-Glycan Site-Specific HeterogeneityR01GM130915 · NIGMS · UNIVERSITY OF GEORGIA · PI KANNAN, NATARAJAN, MOREMEN, KELLEY W. · 2019 to 2022
$3.4M
Acquisition of a 300 kV Electron Microscope for Structural BiologyS10OD021600 · OD · STANFORD UNIVERSITY · PI CHIU, WAH · 2016 to 2016
$2.0M
Understanding human TRPV1 polymodal activationR01NS119505 · NINDS · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI Wade D. Van Horn · 2022 to 2026
$1.9M
NIAID NIH HHS R01 AI148382NIGMS NIH HHS R01 GM080139NIGMS NIH HHS R01 GM130915NIH HHS S10 OD021600NINDS NIH HHS R01 NS119505
6 · The paper itself

Abstract

Coronavirus spike glycoproteins presented on the virion surface mediate receptor binding, and membrane fusion during virus entry and constitute the primary target for vaccine and drug development. How the structure dynamics of the full-length spikes incorporated in viral lipid envelope correlates with the virus infectivity remains poorly understood. Here we present structures and distributions of native spike conformations on vitrified human coronavirus NL63 (HCoV-NL63) virions without chemical fixation by cryogenic electron tomography (cryoET) and subtomogram averaging, along with site-specific glycan composition and occupancy determined by mass spectroscopy. The higher oligomannose glycan shield on HCoV-NL63 spikes than on SARS-CoV-2 spikes correlates with stronger immune evasion of HCoV-NL63. Incorporation of cryoET-derived native spike conformations into all-atom molecular dynamic simulations elucidate the conformational landscape of the glycosylated, full-length spike that reveals a novel role of stalk glycans in modulating spike bending. We show that glycosylation at N1242 at the upper portion of the stalk is responsible for the extensive orientational freedom of the spike crown. Subsequent infectivity assays support the hypothesis that this glycan-dependent motion impacts virus entry. Our results suggest a potential therapeutic target site for HCoV-NL63.

Indexed as

coronaviruscryoETglycaninfectivitymass spectroscopymolecular dynamics

Identifiers

PMID36824920
PMCPMC9949256
OpenAlexW4320920657

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.