Refinement of a cryo-EM structure of hERG: Bridging structure and function.
Biophys J
; 120(4): 738-748, 2021 02 16.
Article
en En
| MEDLINE
| ID: mdl-33476597
ABSTRACT
The human-ether-a-go-go-related gene (hERG) encodes the voltage-gated potassium channel (KCNH2 or Kv11.1, commonly known as hERG). This channel plays a pivotal role in the stability of phase 3 repolarization of the cardiac action potential. Although a high-resolution cryo-EM structure is available for its depolarized (open) state, the structure surprisingly did not feature many functionally important interactions established by previous biochemical and electrophysiology experiments. Using molecular dynamics flexible fitting (MDFF), we refined the structure and recovered the missing functionally relevant salt bridges in hERG in its depolarized state. We also performed electrophysiology experiments to confirm the functional relevance of a novel salt bridge predicted by our refinement protocol. Our work shows how refinement of a high-resolution cryo-EM structure helps to bridge the existing gap between the structure and function in the voltage-sensing domain (VSD) of hERG.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Canales de Potasio Éter-A-Go-Go
/
Simulación de Dinámica Molecular
Límite:
Humans
Idioma:
En
Revista:
Biophys J
Año:
2021
Tipo del documento:
Article
País de afiliación:
Canadá