Alternate splicing of dysferlin C2A confers Ca²âº-dependent and Ca²âº-independent binding for membrane repair.
Structure
; 22(1): 104-15, 2014 Jan 07.
Article
em En
| MEDLINE
| ID: mdl-24239457
ABSTRACT
Dysferlin plays a critical role in the Ca²âº-dependent repair of microlesions that occur in the muscle sarcolemma. Of the seven C2 domains in dysferlin, only C2A is reported to bind both Ca²âº and phospholipid, thus acting as a key sensor in membrane repair. Dysferlin C2A exists as two isoforms, the "canonical" C2A and C2A variant 1 (C2Av1). Interestingly, these isoforms have markedly different responses to Ca²âº and phospholipid. Structural and thermodynamic analyses are consistent with the canonical C2A domain as a Ca²âº-dependent, phospholipid-binding domain, whereas C2Av1 would likely be Ca²âº-independent under physiological conditions. Additionally, both isoforms display remarkably low free energies of stability, indicative of a highly flexible structure. The inverted ligand preference and flexibility for both C2A isoforms suggest the capability for both constitutive and Ca²âº-regulated effector interactions, an activity that would be essential in its role as a mediator of membrane repair.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sarcolema
/
RNA Mensageiro
/
Cálcio
/
Processamento Alternativo
/
Proteínas de Membrana
/
Proteínas Musculares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Structure
Ano de publicação:
2014
Tipo de documento:
Article