The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Molecular Simulations Meet Personalized Medicine. The Mechanism of Action of ClC-5 Antiporter and the Origin of Dent’s Disease
Open accessPreprint — published as 10.1093/pnasnexus/pgaf353 · Paper page
Abstract
ClC-5 is a Cl−/H+ antiporter crucial for the homeostasis of the entire organism, and whose functional deficiencies cause pathologies such as Dent’s disease, a rare genetic disorder that can have lethal consequences. While the clinical aspects of the pathology are known, its molecular basis is elusive, which hampers the development of potential therapies. We present here a systematic study, where we explore the mechanism of transport of ClC-5, deciphering the choreography of structural changes required for the transport of chloride ions and protons in opposing directions. Once the mechanism is determined, we explore how the 523ΔVal deletion linked to Dent’s disease hampers the correct functioning of the transporter, despite having a very minor structural impact. Our study highlights how state-of-the-art simulation methods can provide information on the origin of rare diseases and serve as a tool in personalized medicine.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Flagged first, then by citations
Research works printed but not linked: 39
- 10.1016/j.ceca.2014.09.007 · DOI
- 10.1093/hmg/ddab131 · DOI
- 2009, Mutational Analysis of CLC-5, Cofilin and CLC-4 in Patients with Dent’s Disease, Nephron Physiol, 112, p53, 10.1159/000225944 · DOI
- 10.1007/s00439-020-02219-2 · DOI
- 10.1016/j.bpj.2012.03.067 · DOI
- 10.1371/journal.pbio.3000218 · DOI
- 10.1038/nature20812 · DOI
- 10.1126/science.1195230 · DOI
- 10.1038/415287a · DOI
- Park, E. & MacKinnon, R. Structure of the CLC-1 chloride channel from Homo sapiens. Elife 7, (2018). · DOI
- 10.1126/science.1082708 · DOI
- Miller, C. Q-cubed mutant cues clues to CLC antiport mechanism. Journal of General Physiology 153, (2021). · DOI
- Chavan, T. S. et al. A CLC-ec1 mutant reveals global conformational change and suggests a unifying mechanism for the CLC Cl–/H+ transport cycle. Elife 9, (2020). · DOI
- Khantwal, C. M. et al. Revealing an outward-facing open conformational state in a CLC Cl–/H+ exchange transporter. Elife 5, (2016). · DOI
- 10.1038/nsmb.2814 · DOI
- 10.1016/j.bpj.2009.04.038 · DOI
- 10.1021/jacs.7b11463 · DOI
- 10.1002/prot.21441 · DOI
- 10.1021/bi1019258 · DOI
- Leisle, L. et al. Divergent Cl- and H+ pathways underlie transport coupling and gating in CLC exchangers and channels. Elife 9, (2020). · DOI
- 10.1021/jacs.6b06683 · DOI
- 2013, Dent’s disease: Identification of seven new pathogenic mutations in the CLCN5 gene, J Pediatr Genet, 2, 133
- 10.1016/S0272-6386(01)80067-6 · DOI
- 10.3390/ijms25158110 · DOI
- 10.1101/2021.10.04.463034 · DOI · Paper page
- 10.1038/S41592-022-01488-1 · DOI · Paper page
- 10.1145/3093338.3093390 · DOI
- 10.1093/nar/gki464 · DOI
- 10.1002/jcc.23702 · DOI
- 10.1002/jcc.23354 · DOI
- 10.1063/1.445869 · DOI
- Abraham, M. J. et al. Gromacs: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1–2, 19–25 (2015). · DOI · Paper page
- 10.1093/bioinformatics/bty386 · DOI
- 10.1103/PhysRevLett.100.020603 · DOI · Paper page
- 2006, Efficient reconstruction of complex free energy landscapes by multiple walkers metadynamics, Journal of Physical Chemistry B, 110, 3533, 10.1021/jp054359r · DOI
- 10.1002/prot.1159 · DOI
- 2015, A time-independent free energy estimator for metadynamics, Journal of Physical Chemistry B, 119, 736, 10.1021/jp504920s · DOI
- 10.1186/1471-2105-10-168 · DOI
- 10.1093/bioinformatics/btr550 · DOI
Metadata
- Authors
- Macaluso, V., Pérez, C., Soliva, R., Westermaier, Y., Díaz, L., Wieczór, M., & Orozco, M.
- Affiliations
- Institute for Research in Biomedicine (ES)
- Gdańsk University of Technology (PL)
- Corresponding author
- Orozco, Modesto
- ORCID
- Venue
- PNAS Nexus
- Publisher
- openRxiv
- Published
- 2024-11-08
- Volume
- 4
- Issue
- 11
- Pages
- pgaf353-pgaf353
- ISSN
- 2752-6542 (ISSN-L)
- PMC
- PMC12624513
- OpenAlex
- W4415862285
- Cited by
- 1
- References
- 1
- Citations by year
- 2026: 1
- FWCI
- 0.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PNAS Nexus (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by)
- Funders
- European Regional Development Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- ClC-5, Dent's disease, ion transport mechanism, rare genetic disorders, personalized medicine, molecular simulation, chloride homeostasis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
