Nanomolar affinity of EF-hands in neuronal calcium sensor 1 for bivalent cations Pb2+, Mn2+, and Hg2.
EF-hands
calcium
fluorescence
metal binding
neuronal calcium sensor 1
non-physiological metals
Journal
Metallomics : integrated biometal science
ISSN: 1756-591X
Titre abrégé: Metallomics
Pays: England
ID NLM: 101478346
Informations de publication
Date de publication:
08 07 2022
08 07 2022
Historique:
received:
04
01
2022
accepted:
31
05
2022
pubmed:
4
6
2022
medline:
12
7
2022
entrez:
3
6
2022
Statut:
ppublish
Résumé
Abiogenic metals Pb and Hg are highly toxic since chronic and/or acute exposure often leads to severe neuropathologies. Mn2+ is an essential metal ion but in excess can impair neuronal function. In this study, we address in vitro the interactions between neuronal calcium sensor 1 (NCS1) and divalent cations. Results showed that non-physiological ions (Pb2+ and Mn2+) bind to EF-hands in NCS1 with nanomolar affinity and lower equilibrium dissociation constant than the physiological Ca2+ ion. (Kd, Pb2+ = 7.0 ± 1.0 nM; Kd, Mn2+ = 34.0 ± 6.0 nM; K). Native ultra-high resolution mass spectrometry (FT-ICR MS) and trapped ion mobility spectrometry-mass spectrometry (nESI-TIMS-MS) studies provided the NCS1-metal complex compositions-up to four Ca2+ or Mn2+ ions and three Pb2+ ions (M⋅Pb1-3Ca1-3, M⋅Mn1-4Ca1-2, and M⋅Ca1-4) were observed in complex-and similarity across the mobility profiles suggests that the overall native structure is preserved regardless of the number and type of cations. However, the non-physiological metal ions (Pb2+, Mn2+, and Hg2+) binding to NCS1 leads to more efficient quenching of Trp emission and a decrease in W30 and W103 solvent exposure compared to the apo and Ca2+ bound form, although the secondary structural rearrangement and exposure of hydrophobic sites are analogous to those for Ca2+ bound protein. Only Pb2+ and Hg2+ binding to EF-hands leads to the NCS1 dimerization whereas Mn2+ bound NCS1 remains in the monomeric form, suggesting that other factors in addition to metal ion coordination, are required for protein dimerization.
Identifiants
pubmed: 35657675
pii: 6601456
doi: 10.1093/mtomcs/mfac039
pmc: PMC9611292
pii:
doi:
Substances chimiques
Cations, Divalent
0
Neuronal Calcium-Sensor Proteins
0
Neuropeptides
0
frequenin calcium sensor proteins
0
Lead
2P299V784P
Manganese
42Z2K6ZL8P
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM134247
Pays : United States
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press.
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