Interaction between the Linker, Pre-S1, and TRP Domains Determines Folding, Assembly, and Trafficking of TRPV Channels
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Archivos
Fecha
2015-08
Profesor/a Guía
Facultad/escuela
Idioma
en
Título de la revista
ISSN de la revista
Título del volumen
Editor
Cell Press
Nombre de Curso
Licencia CC
Atribución 4.0 Internacional (CC BY 4.0)
Licencia CC
https://creativecommons.org/licenses/by/4.0/deed.es
Resumen
Summary Functional transient receptor potential (TRP) channels result from the assembly of four subunits. Here, we show an interaction between the pre-S1, TRP, and the ankyrin repeat domain (ARD)-S1 linker domains of TRPV1 and TRPV4 that is essential for proper channel assembly. Neutralization of TRPV4 pre-S1 K462 resulted in protein retention in the ER, defective glycosylation and trafficking, and unresponsiveness to TRPV4-activating stimuli. Similar results were obtained with the equivalent mutation in TRPV1 pre-S1. Molecular dynamics simulations revealed that TRPV4-K462 generated an alternating hydrogen network with E745 (TRP box) and D425 (pre-S1 linker), and that K462Q mutation affected subunit folding. Consistently, single TRPV4-E745A or TRPV4-D425A mutations moderately affected TRPV4 biogenesis while double TRPV4-D425A/E745A mutation resumed the TRPV4-K462Q phenotype. Thus, the interaction between pre-S1, TRP, and linker domains is mandatory to generate a structural conformation that allows the contacts between adjacent subunits to promote correct assembly and trafficking to the plasma membrane. © 2015 Elsevier Ltd.
Notas
Indexación: Scopus
Palabras clave
Transient Receptor Potential Channels, Animals, RN 1734
Citación
Structure Volume 23, Issue 8, Pages 1404 - 14137 August 2015 Article number 3202
DOI
10.1016/j.str.2015.05.018