Structure of the human plasma membrane Ca2+-ATPase 1 in complex with its obligatory subunit neuroplastin.
Nat Commun
; 9(1): 3623, 2018 09 06.
Article
em En
| MEDLINE
| ID: mdl-30190470
ABSTRACT
Plasma membrane Ca2+-ATPases (PMCAs) are key regulators of global Ca2+ homeostasis and local intracellular Ca2+ dynamics. Recently, Neuroplastin (NPTN) and basigin were identified as previously unrecognized obligatory subunits of PMCAs that dramatically increase the efficiency of PMCA-mediated Ca2+ clearance. Here, we report the cryo-EM structure of human PMCA1 (hPMCA1) in complex with NPTN at a resolution of 4.1 Å for the overall structure and 3.9 Å for the transmembrane domain. The single transmembrane helix of NPTN interacts with the TM8-9-linker and TM10 of hPMCA1. The subunits are required for the hPMCA1 functional activity. The NPTN-bound hPMCA1 closely resembles the E1-Mg2+ structure of endo(sarco)plasmic reticulum Ca2+ ATPase and the Ca2+ site is exposed through a large open cytoplasmic pathway. This structure provides insight into how the subunits bind to the PMCAs and serves as an important basis for understanding the functional mechanisms of this essential calcium pump family.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
/
ATPases Transportadoras de Cálcio da Membrana Plasmática
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article