What ATP binding does to the Ca2+ pump and how nonproductive phosphoryl transfer is prevented in the absence of Ca2.
Proc Natl Acad Sci U S A
; 117(31): 18448-18458, 2020 08 04.
Article
em En
| MEDLINE
| ID: mdl-32675243
ABSTRACT
Under physiological conditions, most Ca2+-ATPase (SERCA) molecules bind ATP before binding the Ca2+ transported. SERCA has a high affinity for ATP even in the absence of Ca2+, and ATP accelerates Ca2+ binding at pH values lower than 7, where SERCA is in the E2 state with low-affinity Ca2+-binding sites. Here we describe the crystal structure of SERCA2a, the isoform predominant in cardiac muscle, in the E2·ATP state at 3.0-Å resolution. In the crystal structure, the arrangement of the cytoplasmic domains is distinctly different from that in canonical E2. The A-domain now takes an E1 position, and the N-domain occupies exactly the same position as that in the E1·ATP·2Ca2+ state relative to the P-domain. As a result, ATP is properly delivered to the phosphorylation site. Yet phosphoryl transfer never takes place without the filling of the two transmembrane Ca2+-binding sites. The present crystal structure explains what ATP binding itself does to SERCA and how nonproductive phosphorylation is prevented in E2.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Trifosfato de Adenosina
/
Cálcio
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ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article