dc.contributor.author | Lian, Lu-Yun | |
dc.contributor.author | Pandalaneni, Sravan R. | |
dc.contributor.author | Patel, Pryank | |
dc.contributor.author | McCue, Hannah V. | |
dc.contributor.author | Haynes, Lee P. | |
dc.contributor.author | Burgoyne, Robert D. | |
dc.date.accessioned | 2016-03-16T10:14:59Z | |
dc.date.available | 2016-03-16T10:14:59Z | |
dc.date.issued | 2011-11-16 | |
dc.identifier.citation | Lian , L-Y , Pandalaneni , S R , Patel , P , McCue , H V , Haynes , L P & Burgoyne , R D 2011 , ' Characterisation of the interaction of the C-terminus of the dopamine D2 receptor with neuronal calcium sensor-1 ' , PLoS ONE , vol. 6 , no. 11 , pp. e27779 . https://doi.org/10.1371/journal.pone.0027779 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/2299/16800 | |
dc.description | Copyright: © 2011 Lian et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited | |
dc.description.abstract | NCS-1 is a member of the neuronal calcium sensor (NCS) family of EF-hand Ca(2+) binding proteins which has been implicated in several physiological functions including regulation of neurotransmitter release, membrane traffic, voltage gated Ca(2+) channels, neuronal development, synaptic plasticity, and learning. NCS-1 binds to the dopamine D2 receptor, potentially affecting its internalisation and controlling dopamine D2 receptor surface expression. The D2 receptor binds NCS-1 via a short 16-residue cytoplasmic C-terminal tail. We have used NMR and fluorescence spectroscopy to characterise the interactions between the NCS-1/Ca(2+) and D2 peptide. The data show that NCS-1 binds D2 peptide with a K(d) of ∼14.3 µM and stoichiometry of peptide binding to NCS-1 of 2:1. NMR chemical shift mapping confirms that D2 peptide binds to the large, solvent-exposed hydrophobic groove, on one face of the NCS-1 molecule, with residues affected by the presence of the peptide spanning both the N and C-terminal portions of the protein. The NMR and mutagenesis data further show that movement of the C-terminal helix 11 of NCS-1 to fully expose the hydrophobic groove is important for D2 peptide binding. Molecular docking using restraints derived from the NMR chemical shift data, together with the experimentally-derived stoichiometry, produced a model of the complex between NCS-1 and the dopamine receptor, in which two molecules of the receptor are able to simultaneously bind to the NCS-1 monomer. | en |
dc.format.extent | 1311685 | |
dc.language.iso | eng | |
dc.relation.ispartof | PLoS ONE | |
dc.subject | Amino Acid Sequence | |
dc.subject | Animals | |
dc.subject | Calcium Signaling | |
dc.subject | Humans | |
dc.subject | Magnetic Resonance Spectroscopy | |
dc.subject | Models, Molecular | |
dc.subject | Molecular Sequence Data | |
dc.subject | Neuronal Calcium-Sensor Proteins | |
dc.subject | Neuropeptides | |
dc.subject | Peptide Fragments | |
dc.subject | Protein Binding | |
dc.subject | Protein Multimerization | |
dc.subject | Protein Structure, Tertiary | |
dc.subject | Rats | |
dc.subject | Receptors, Dopamine D2 | |
dc.title | Characterisation of the interaction of the C-terminus of the dopamine D2 receptor with neuronal calcium sensor-1 | en |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Biosciences Research Group | |
dc.contributor.institution | Centre for Research in Mechanisms of Disease and Drug Discovery | |
dc.contributor.institution | Department of Clinical, Pharmaceutical and Biological Science | |
dc.contributor.institution | Centre for Future Societies Research | |
dc.description.status | Peer reviewed | |
rioxxterms.versionofrecord | 10.1371/journal.pone.0027779 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |