Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/225156
Molecular simulations meet personalized medicine: The mechanism of action of CLC-5 antiporter and the origin of Dent's disease
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
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 523 Delta Val 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 shed light on the origin of rare diseases and explore targets for personalized medicine.
Matèries (anglès)
Citació
Citació
MACALUSO, Veronica, et al. Molecular simulations meet personalized medicine: The mechanism of action of CLC-5 antiporter and the origin of Dent's disease. PNAS Nexus. 2025. Vol. 4, num. 11, pags. pgaf353. ISSN 2752-6542. [consulted: 4 of August of 2026]. Available at: https://hdl.handle.net/2445/225156