Comparing the structure and dynamics of phospholamban pentamer in its unphosphorylated and pseudo-phosphorylated states.
Protein Sci
; 16(9): 1977-83, 2007 Sep.
Article
en En
| MEDLINE
| ID: mdl-17766390
ABSTRACT
Human phospholamban (PLN), a 30 kDa homopentamer in the sarcoplasmic reticulum (SR) membrane, controls the magnitude of heart muscle contraction and relaxation by regulating the calcium pumping activity of the SR Ca(2+)-ATPase (SERCA). When PLN is not phosphorylated, it binds and inhibits SERCA. Phosphorylation of PLN at S16 or T17 releases such inhibitory effect. It remains a matter of debate whether phosphorylation perturbs the structure of PLN, which in turn affects its interaction with SERCA. Here we examine by NMR spectroscopy the structure and dynamics of PLN pentamer with a physiologically relevant, phosphorylation-mimicking mutation, S16E. Based on extensive NMR data, including NOEs, dipolar couplings, and solvent exchange of backbone amides, we conclude that the phosphorylation-mimicking mutation does not perturb the pentamer structure. However, (15)N R(1) and R(2) relaxation rates and (15)N((1)H) NOEs suggest subtle differences in the dynamics of the extramembrane portion of the protein.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas de Unión al Calcio
Límite:
Humans
Idioma:
En
Revista:
Protein Sci
Asunto de la revista:
BIOQUIMICA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos