Backbone and side-chain resonance assignments of (Ca2+)4-calmodulin bound to beta calcineurin A CaMBD peptide.
Biomol NMR Assign
; 11(2): 275-280, 2017 Oct.
Article
em En
| MEDLINE
| ID: mdl-28815458
ABSTRACT
Calcineurin (CaN) is a heterodimeric and highly conserved serine/threonine phosphatase (PP2B) that plays a critical role in coupling calcium signals to physiological processes including embryonic cardiac development, NF-AT-regulated gene expression in immune responses, and apoptosis. The catalytic subunit (CaNA) has three isoforms (α, ß, and γ,) in humans and seven isoforms in Paramecium. In all eukaryotes, the EF-hand protein calmodulin (CaM) regulates CaN activity in a calcium-dependent manner. The N- and C-domains of CaM (CaMN and CaMC) recognize a CaM-binding domain (CaMBD) within an intrinsically disordered region of CaNA that precedes the auto-inhibitory domain (AID) of CaNA. Here we present nearly complete 1H, 13C, and 15N resonance assignments of (Ca2+)4-CaM bound to a peptide containing the CaMBD sequence in the beta isoform of CaNA (ßCaNA-CaMBDp). Its secondary structure elements predicted from the assigned chemical shifts were in good agreement with those observed in the high-resolution structures of (Ca2+)4-CaM bound to CaMBDs of multiple enzymes. Based on the reported literature, the CaMBD of the α isoform of CaNA can bind to CaM in two opposing orientations which may influence the regulatory function of CaM. Because a high resolution structure of (Ca2+)4-CaM bound to ßCaNA-CaMBDp has not been reported, our studies serve as a starting point for determining the solution structure of this complex. This will demonstrate the preferred orientation of (Ca2+)4-CaM on the CaMBD as well as the orientations of CaMN and CaMC relative to each other and to the AID of ßCaNA.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Calmodulina
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Cálcio
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Calcineurina
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Ressonância Magnética Nuclear Biomolecular
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Biomol NMR Assign
Assunto da revista:
BIOLOGIA MOLECULAR
/
MEDICINA NUCLEAR
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos