Calmodulin confers calcium sensitivity to the stability of the distal intracellular assembly domain of Kv7.2 channels.
Sci Rep
; 7(1): 13425, 2017 10 18.
Article
en En
| MEDLINE
| ID: mdl-29044210
ABSTRACT
Tetrameric coiled-coil structures are present in many ion channels, often adjacent to a calmodulin (CaM) binding site, although the relationship between the two is not completely understood. Here we examine the dynamic properties of the ABCD domain located in the intracellular C-terminus of tetrameric, voltage-dependent, potassium selective Kv7.2 channels. This domain encompasses the CaM binding site formed by helices A and B, followed by helix C, which is linked to the helix D coiled-coil. The data reveals that helix D stabilizes CaM binding, promoting trans-binding (CaM embracing neighboring subunits), and they suggest that the ABCD domain can be exchanged between subunits of the tetramer. Exchange is faster when mutations in AB weaken the CaM interaction. The exchange of ABCD domains is slower in the presence of Ca2+, indicating that CaM stabilization of the tetrameric assembly is enhanced when loaded with this cation. Our observations are consistent with a model that involves a dynamic mechanism of helix D assembly, which supports reciprocal allosteric coupling between the A-B module and the coiled-coil formed by the helix D. Thus, formation of the distal helix D tetramer influences CaM binding and CaM-dependent Kv7.2 properties, whereas reciprocally, CaM and Ca2+ influence the dynamic behavior of the helix D coiled-coil.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Calmodulina
/
Calcio
/
Canal de Potasio KCNQ2
/
Multimerización de Proteína
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Sci Rep
Año:
2017
Tipo del documento:
Article
País de afiliación:
España