Evidence map›Paper›PMID 35072004›Full record

ArticleiScience2022

Molecular dynamics and functional characterization of I37R-CFTR lasso mutation provide insights into channel gating activity.

Sharon L Wong, Nikhil T Awatade, Miro A Astore, Katelin M Allan, Michael J Carnell, Iveta Slapetova, Po-Chia Chen, Alexander Capraro, Laura K Fawcett, Renee M Whan and 5 more

Open access · goldAbstract read
In one paragraph

Article in iScience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

8 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Gas-modulating microcapsules for spatiotemporal control of hypoxia.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  5. Q1291H-CFTR molecular dynamics simulations andFrontiers in molecular biosciences · 2023
    Article
  6. Review
  7. Article
  8. 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

15 authors at 2 institutions in 1 country.

Sharon L WongSchool of Women's and Children's Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, Australia.
Nikhil T AwatadeSchool of Women's and Children's Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, Australia.
Miro A AstoreSchool of Physics, University of Sydney, Sydney, Australia.
Katelin M AllanSchool of Women's and Children's Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, Australia.
Michael J CarnellKatharina Gaus Light Microscopy Facility, Mark Wainwright Analytical Centre, UNSW Sydney, Sydney, Australia.
Iveta SlapetovaKatharina Gaus Light Microscopy Facility, Mark Wainwright Analytical Centre, UNSW Sydney, Sydney, Australia.
Po-Chia ChenSchool of Physics, University of Sydney, Sydney, Australia.
Alexander CapraroSchool of Women's and Children's Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, Australia.
Laura K FawcettSchool of Women's and Children's Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, Australia.
Renee M WhanKatharina Gaus Light Microscopy Facility, Mark Wainwright Analytical Centre, UNSW Sydney, Sydney, Australia.
Renate GriffithSchool of Chemistry, UNSW Sydney, Sydney, Australia.
Chee Y OoiSchool of Women's and Children's Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, Australia.
Serdar KuyucakSchool of Physics, University of Sydney, Sydney, Australia.
Adam JaffeSchool of Women's and Children's Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, Australia.
Shafagh A WatersSchool of Women's and Children's Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, Australia.
UNSW Sydney · AUThe University of Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Characterization of I37R, a mutation located in the lasso motif of the CFTR chloride channel, was conducted by theratyping several CFTR modulators from both potentiator and corrector classes. Intestinal current measurements in rectal biopsies, forskolin-induced swelling (FIS) in intestinal organoids, and short circuit current measurements in organoid-derived monolayers from an individual with I37R/F508del CFTR genotype demonstrated that the I37R-CFTR results in a residual function defect amenable to treatment with potentiators and type III, but not type I, correctors. Molecular dynamics of I37R using an extended model of the phosphorylated, ATP-bound human CFTR identified an altered lasso motif conformation which results in an unfavorable strengthening of the interactions between the lasso motif, the regulatory (R) domain, and the transmembrane domain 2 (TMD2). Structural and functional characterization of the I37R-

Indexed as

BiochemistryPharmacologyStructural biology

Identifiers

PMID35072004
PMCPMC8761696
OpenAlexW4205620448

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.