Evidence map›Paper›PMID 30737386›Full record

ArticleNature communications2019

Selection of immunoglobulin elbow region mutations impacts interdomain conformational flexibility in HIV-1 broadly neutralizing antibodies.

Rory Henderson, Brian E Watts, Hieu N Ergin, Kara Anasti, Robert Parks, Shi-Mao Xia, Ashley Trama, Hua-Xin Liao, Kevin O Saunders, Mattia Bonsignori and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

28 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
  2. Article
  3. Explore antibody repertoire in the era of AI.Acta biochimica et biophysica Sinica · 2025
    Article
  4. Article
  5. Article
  6. The CH1 domain influences the expression and antigen sensing of the HIV-specific CH31 IgM-BCR and IgG-BCR.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  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

13 authors at 2 institutions in 2 countries.

Rory HendersonDepartment of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
Brian E WattsDepartment of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
Hieu N ErginDepartment of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
Kara AnastiDepartment of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
Robert ParksDepartment of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
Shi-Mao XiaDepartment of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
Ashley TramaDepartment of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
Hua-Xin LiaoDepartment of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
Kevin O SaundersDepartment of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.ORCID http://orcid.org/0000-0001-7399-7954
Mattia BonsignoriDepartment of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
Kevin WieheDepartment of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
Barton F HaynesDepartment of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
S Munir AlamDepartment of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA. munir.alam@duke.edu.
Duke University · USJinan University · CN

Funding

Virus biology scientific research support componentUM1AI100645 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2012 to 2018
$204.7M
Ruth L. Kirschstein National Research Service Award (NRSA)- T32T32AI007392 · NIAID · DUKE UNIVERSITY · PI Amy Lynn Corneli, Guido Ferrari · 1990 to 2026
$9.8M
Data commons for 'omic, microscopy and analysis core facilitiesS10OD018164 · OD · DUKE UNIVERSITY · PI WRAY, GREGORY A. · 2014 to 2014
$598k
NIAID NIH HHS T32 AI007392NIAID NIH HHS UM1 AI100645NIH HHS S10 OD018164
6 · The paper itself

Abstract

Somatic mutations within antibody variable and framework regions (FWR) can alter thermostability and structural flexibility, but their impact on functional potency is unclear. Here we study thermostability and use molecular dynamics (MD) simulations to assess the role of FWR mutations during maturation of HIV-1 broadly neutralizing antibodies (bnAbs). The tested bnAbs show lower thermostability than their unmutated ancestor antibodies. FWR mutations in the Fab elbow region are frequently observed in HIV-1 bnAbs and MD simulations show that such FWR mutations alter interdomain flexibility in two HIV-1 bnAbs. In a CD4-binding site lineage, reversion mutations result in a loss of neutralization potency in an early intermediate and affinity-matured bnAb against autologous and heterologous Tier-2 viruses, respectively. Elbow region reversion mutations in a glycan-V3 bnAb modestly reduces potency against an autologous virus isolate. Thus, selection of mutations in the Fab elbow region impacts interdomain conformational flexibility and paratope plasticity during bnAb development.

Indexed as

Antibodies, NeutralizingCalorimetry, Differential ScanningCircular DichroismHIV-1HIV AntibodiesHumansMolecular Dynamics SimulationMutationNeutralization TestsSurface Plasmon ResonanceAntibodies, NeutralizingHIV Antibodies

Identifiers

PMID30737386
PMCPMC6368608
OpenAlexW2912640294

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.