A transistor model for the cystic fibrosis transmembrane conductance regulator.
Journal
Biophysical reports
ISSN: 2667-0747
Titre abrégé: Biophys Rep (N Y)
Pays: United States
ID NLM: 9918266001106676
Informations de publication
Date de publication:
14 Jun 2023
14 Jun 2023
Historique:
received:
08
12
2022
accepted:
07
04
2023
medline:
23
6
2023
pubmed:
23
6
2023
entrez:
23
6
2023
Statut:
epublish
Résumé
In this paper we present a transistor circuit model for cystic fibrosis transmembrane conductance regulator (CFTR) that seeks to map the functional form of CFTR both in wild type and mutants. The circuit architecture is configured so that the function, and as much as possible the form, faithfully represents what is known about CFTR from cryo-electron microscopy and molecular dynamics. The model is a mixed analog-digital topology with an AND gate receiving the input from two separate ATP-nucleotide-binding domain binding events. The analog portion of the circuit takes the output from the AND gate as its input. The input to the circuit model and its noise characteristics are extracted from single-channel patch-clamp experiments. The chloride current predicted by the model is then compared with single-channel patch-clamp recordings for wild-type CFTR. We also consider the patch-clamp recordings from CFTR with a G551D point mutation, a clinically relevant mutant that is responsive to therapeutic management. Our circuit model approach enables bioengineering approaches to CFTR and allows biophysicists to use efficient circuit simulation tools to analyze its behavior.
Identifiants
pubmed: 37351179
doi: 10.1016/j.bpr.2023.100108
pii: S2667-0747(23)00009-5
pmc: PMC10282560
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100108Informations de copyright
© 2023 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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