title: Membrane binding of Neuronal Calcium Sensor-1 (NCS1).
abstract: Neuronal Calcium Sensor-1 (NCS1) belongs to the family of Neuronal Calcium Sensor (NCS) proteins. NCS1 is composed of four EF-hand motifs and an N-terminal myristoylation. However, the presence of a calcium-myristoyl switch in NCS1 and its role in the membrane binding are controversial. The model of Langmuir lipid monolayers is thus used to mimic the cell membrane in order to characterize the membrane interactions of NCS1. Two binding parameters are calculated from monolayer measurements: the maximum insertion pressure, up to which protein binding is energetically favorable, and the synergy, reporting attractive or repulsive interactions with the lipid monolayers. Binding membrane measurements performed in the presence of myristoylated NCS1 reveal better binding interactions for phospholipids composed of phosphoethanolamine polar head groups and unsaturated fatty acyl chains. In the absence of calcium, the membrane binding measurements are drastically modified and suggest that the protein is more strongly bound to the membrane. Indeed, the binding of calcium by three EF-hand motifs of NCS1 leads to a conformation change. NCS1 arrangement at the membrane could thus be reshuffled for better interactions with its substrates. The N-terminal peptide of NCS1 is composed of two amphiphilic helices involved in the membrane interactions of NCS1. Moreover, the presence of the myristoyl group has a weak influence on the membrane binding of NCS1 suggesting the absence of a calcium-myristoyl switch mechanism in this protein. The myristoylation could thus have a structural role required in the folding/unfolding of NCS1 which is essential to its multiple biological functions.
authors.affiliation: CUO-Recherche, Hôpital du Saint-Sacrement, Centre de recherche du CHU de Québec and Département d'ophtalmologie, Faculté de médecine, Université Laval, Québec, Québec, Canada.
authors.forename: Samuel
authors.initials: S
authors.lastname: Lemire
authors.affiliation: Banyan Biomarkers Inc., Alachua, FL, United States.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jeromin
authors.affiliation: CUO-Recherche, Hôpital du Saint-Sacrement, Centre de recherche du CHU de Québec and Département d'ophtalmologie, Faculté de médecine, Université Laval, Québec, Québec, Canada. Electronic address: Elodie.Boisselier@fmed.ulaval.ca.
authors.forename: Élodie
authors.initials: É
authors.lastname: Boisselier
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D004983:Ethanolamines / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019814:Myristic Acid / Q000378:metabolism; D051580:Neuronal Calcium-Sensor Proteins / Q000737:chemistry* / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry* / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D012568:Schizosaccharomyces / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D002135:Calcium-Binding Proteins; D004983:Ethanolamines; C400903:FRQ1 protein, S cerevisiae; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D010743:Phospholipids; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C101464:frequenin calcium sensor proteins; D019814:Myristic Acid; C005448:phosphorylethanolamine; D002118:Calcium
keywords: Calcium–myristoyl switch; Langmuir monolayers; Membrane binding; Myristoylation; Neuronal Calcium Sensor-1; Phospholipids