Evidence map›Paper›PMID 33619492›Full record

ArticlebioRxiv : the preprint server for biology2021

A glycan gate controls opening of the SARS-CoV-2 spike protein.

Terra Sztain, Surl-Hee Ahn, Anthony T Bogetti, Lorenzo Casalino, Jory A Goldsmith, Evan Seitz, Ryan S McCool, Fiona L Kearns, Francisco Acosta-Reyes, Suvrajit Maji and 7 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Terra Sztain *Department of Chemistry and Biochemistry, UC San Diego, La Jolla, CA 92093.
Surl-Hee Ahn *Department of Chemistry and Biochemistry, UC San Diego, La Jolla, CA 92093.
Anthony T BogettiDepartment of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260.
Lorenzo CasalinoDepartment of Chemistry and Biochemistry, UC San Diego, La Jolla, CA 92093.
Jory A GoldsmithDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712.
Evan SeitzDepartment of Biological Sciences, Columbia University, New York, NY, 10032, USA.
Ryan S McCoolDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712.
Fiona L KearnsDepartment of Chemistry and Biochemistry, UC San Diego, La Jolla, CA 92093.
Francisco Acosta-ReyesDepartment of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032, USA.
Suvrajit MajiDepartment of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032, USA.
Ghoncheh MashayekhiDepartment of Physics, University of Wisconsin-Milwaukee, 3135 N. Maryland Ave, Milwaukee, WI 53211, USA.
J Andrew McCammonDepartment of Chemistry and Biochemistry, UC San Diego, La Jolla, CA 92093.
Abbas OurmazdDepartment of Physics, University of Wisconsin-Milwaukee, 3135 N. Maryland Ave, Milwaukee, WI 53211, USA.
Joachim FrankDepartment of Biological Sciences, Columbia University, New York, NY, 10032, USA.
Jason S McLellanDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712.
Lillian T ChongDepartment of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260.
Rommie E AmaroDepartment of Chemistry and Biochemistry, UC San Diego, La Jolla, CA 92093.

Funding

THEORY OF BIOMOLECULAR DIFFUSIONR01GM031749 · NIGMS · UNIVERSITY OF HOUSTON · PI HUBER, GARY ALEXANDER, MCCAMMON, JAMES ANDREW · 1985 to 2022
$7.8M
STRUCTURE ANALYSIS OF MACROMOLECULAR ASSEMBLIESR01GM029169 · NIGMS · WADSWORTH CENTER · PI FRANK, JOACHIM · 1985 to 2019
$6.1M
WESTPA: A high-performance framework for simulating at the frontiers of biologyR01GM115805 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LILLIAN T CHONG · 2015 to 2026
$4.0M
Structural Studies of Macromolecular Assemblies Using Cryo-EMR35GM139453 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI FRANK, JOACHIM · 2021 to 2025
$3.9M
Structure, Function and Antigenicity of Coronavirus Spike ProteinsR01AI127521 · NIAID · UNIVERSITY OF TEXAS AT AUSTIN · PI MCLELLAN, JASON SCOTT, WARD, ANDREW BARRETT · 2017 to 2021
$3.1M
A MULTISCALE APPROACH TO TARGET THE ACHILLES HEEL OF P53 CANCER MUTANTS (Equipment Supplement)R01GM132826 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AMARO, ROMMIE E · 2019 to 2022
$1.3M
NIAID NIH HHS R01 AI127521NIGMS NIH HHS R01 GM029169NIGMS NIH HHS R01 GM031749NIGMS NIH HHS R01 GM115805NIGMS NIH HHS R01 GM132826NIGMS NIH HHS R35 GM139453
6 · The paper itself

Abstract

SARS-CoV-2 infection is controlled by the opening of the spike protein receptor binding domain (RBD), which transitions from a glycan-shielded "down" to an exposed "up" state in order to bind the human ACE2 receptor and infect cells. While snapshots of the "up" and "down" states have been obtained by cryoEM and cryoET, details of the RBD opening transition evade experimental characterization. Here, over 130 μs of weighted ensemble (WE) simulations of the fully glycosylated spike ectodomain allow us to characterize more than 300 continuous, kinetically unbiased RBD opening pathways. Together with ManifoldEM analysis of cryo-EM data and biolayer interferometry experiments, we reveal a gating role for the N-glycan at position N343, which facilitates RBD opening. Residues D405, R408, and D427 also participate. The atomic-level characterization of the glycosylated spike activation mechanism provided herein achieves a new high-water mark for ensemble pathway simulations and offers a foundation for understanding the fundamental mechanisms of SARS-CoV-2 viral entry and infection.

Identifiers

PMID33619492
PMCPMC7899456

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.