Evidence map›Paper›PMID 24224757›Full record

ArticleBiochemistry2013

Molecular mechanisms of inhibition of influenza by surfactant protein D revealed by large-scale molecular dynamics simulation.

Boon Chong Goh, Michael J Rynkiewicz, Tanya R Cafarella, Mitchell R White, Kevan L Hartshorn, Kimberly Allen, Erika C Crouch, Oliviana Calin, Peter H Seeberger, Klaus Schulten and 1 more

Abstract read
In one paragraph

Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
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

21 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. The Role of Glycosylation in Infectious Diseases.Advances in experimental medicine and biology · 2021
    Review
  7. Article
  8. Innate Immunity and Influenza A Virus Pathogenesis: Lessons for COVID-19.Frontiers in cellular and infection microbiology · 2020
    Review
  9. Review
  10. Review
  11. All-atom virus simulations.Current opinion in virology · 2018
    Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Boon Chong GohBeckman Institute and Department of Physics, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
Michael J Rynkiewicz
Tanya R Cafarella
Mitchell R White
Kevan L Hartshorn
Kimberly Allen
Erika C Crouch
Oliviana Calin
Peter H Seeberger
Klaus Schulten
Barbara A Seaton
Max Planck Institute of Colloids and Interfaces · DEUniversity of Illinois Urbana-Champaign · USWashington University in St. Louis · US

Funding

WHOLE CELL SIMULATIONP41GM104601 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI SCHULTEN, KLAUS · 2012 to 2021
$19.0M
Enhancing Collectin-Mediated Defense Against InfluenzaR01HL069031 · NHLBI · BOSTON MEDICAL CENTER · PI HARTSHORN, KEVAN L · 2002 to 2018
$6.6M
Collectins and Innate Defense against Inhaled PathogensP01AI083222 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI SEATON, BARBARA A · 2009 to 2010
$4.9M
NHLBI NIH HHS R01 HL069031NHLBI NIH HHS R01HL069031NIAID NIH HHS P01 AI083222NIAID NIH HHS P01AI083222NIGMS NIH HHS 9P41GM104601NIGMS NIH HHS P41 GM104601
6 · The paper itself

Abstract

Surfactant protein D (SP-D), a mammalian C-type lectin, is the primary innate inhibitor of influenza A virus (IAV) in the lung. Interactions of SP-D with highly branched viral N-linked glycans on hemagglutinin (HA), an abundant IAV envelope protein and critical virulence factor, promote viral aggregation and neutralization through as yet unknown molecular mechanisms. Two truncated human SP-D forms, wild-type (WT) and double mutant D325A+R343V, representing neck and carbohydrate recognition domains are compared in this study. Whereas both WT and D325A+R343V bind to isolated glycosylated HA, WT does not inhibit IAV in neutralization assays; in contrast, D325A+R343V neutralization compares well with that of full-length native SP-D. To elucidate the mechanism for these biochemical observations, we have determined crystal structures of D325A+R343V in the presence and absence of a viral nonamannoside (Man9). On the basis of the D325A+R343V-Man9 structure and other crystallographic data, models of complexes between HA and WT or D325A+R343V were produced and subjected to molecular dynamics. Simulations reveal that whereas WT and D325A+R343V both block the sialic acid receptor site of HA, the D325A+R343V complex is more stable, with stronger binding caused by additional hydrogen bonds and hydrophobic interactions with HA residues. Furthermore, the blocking mechanism of HA differs for WT and D325A+R343V because of alternate glycan binding modes. The combined results suggest a mechanism through which the mode of SP-D-HA interaction could significantly influence viral aggregation and neutralization. These studies provide the first atomic-level molecular view of an innate host defense lectin inhibiting its viral glycoprotein target.

Indexed as

Models, MolecularAdhesivenessAmino Acid SubstitutionBinding SitesHemagglutinin Glycoproteins, Influenza VirusHumansHydrogen BondingHydrophobic and Hydrophilic InteractionsInfluenza A Virus, H3N2 SubtypeMicrobial ViabilityMolecular Dynamics SimulationMutant ProteinsPeptide FragmentsPolysaccharidesProtein ConformationPulmonary Surfactant-Associated Protein DHemagglutinin Glycoproteins, Influenza Virushemagglutinin, human influenza A virusMutant ProteinsPeptide FragmentsPolysaccharidesPulmonary Surfactant-Associated Protein DReceptors, Cell SurfaceRecombinant Proteinssialic acid receptor

Identifiers

PMID24224757
PMCPMC3927399
OpenAlexW1980694919

What OpenQuestion holds

Textmetadata
LicenceTDM
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.