Chemometric Models of Differential Amino Acids at the Navα and Navß Interface of Mammalian Sodium Channel Isoforms.
Molecules
; 25(15)2020 Aug 03.
Article
en En
| MEDLINE
| ID: mdl-32756517
ABSTRACT
(1) Background:
voltage-gated sodium channels (Navs) are integral membrane proteins that allow the sodium ion flux into the excitable cells and initiate the action potential. They comprise an α (Navα) subunit that forms the channel pore and are coupled to one or more auxiliary ß (Navß) subunits that modulate the gating to a variable extent. (2)Methods:
after performing homology in silico modeling for all nine isoforms (Nav1.1α to Nav1.9α), the Navα and Navß protein-protein interaction (PPI) was analyzed chemometrically based on the primary and secondary structures as well as topological or spatial mapping. (3)Results:
our findings reveal a unique isoform-specific correspondence between certain segments of the extracellular loops of the Navα subunits. Precisely, loop S5 in domain I forms part of the PPI and assists Navß1 or Navß3 on all nine mammalian isoforms. The implied molecular movements resemble macroscopic springs, all of which explains published voltage sensor effects on sodium channel fast inactivation in gating. (4)Conclusions:
currently, the specific functions exerted by the Navß1 or Navß3 subunits on the modulation of Navα gating remain unknown. Our work determined functional interaction in the extracellular domains on theoretical grounds and we propose a schematic model of the gating mechanism of fast channel sodium current inactivation by educated guessing.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Modelos Moleculares
/
Canales de Sodio Activados por Voltaje
/
Aminoácidos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Molecules
Asunto de la revista:
BIOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
México