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Neuronal Calcium Sensor-1 Binds the D2 Dopamine Receptor and G-protein-coupled Receptor Kinase 1 (GRK1) Peptides Using Different Modes of Interactions

Neuronal Calcium Sensor-1 Binds the D2 Dopamine Receptor and G-protein-coupled Receptor Kinase 1 (GRK1) Peptides Using Different Modes of Interactions

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PANDALANENI, Sravan, Vijaykumar KARUPPIAH, Muhammad SALEEM, Lee P. HAYNES, Robert D. BURGOYNE, Olga MAYANS, Jeremy P. DERRICK, Lu-Yun LIAN, 2015. Neuronal Calcium Sensor-1 Binds the D2 Dopamine Receptor and G-protein-coupled Receptor Kinase 1 (GRK1) Peptides Using Different Modes of Interactions. In: Journal of Biological Chemistry. 290(30), pp. 18744-18756. ISSN 0021-9258. eISSN 1083-351X

@article{Pandalaneni2015-07-24Neuro-34939, title={Neuronal Calcium Sensor-1 Binds the D2 Dopamine Receptor and G-protein-coupled Receptor Kinase 1 (GRK1) Peptides Using Different Modes of Interactions}, year={2015}, doi={10.1074/jbc.M114.627059}, number={30}, volume={290}, issn={0021-9258}, journal={Journal of Biological Chemistry}, pages={18744--18756}, author={Pandalaneni, Sravan and Karuppiah, Vijaykumar and Saleem, Muhammad and Haynes, Lee P. and Burgoyne, Robert D. and Mayans, Olga and Derrick, Jeremy P. and Lian, Lu-Yun} }

<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/34939"> <dcterms:title>Neuronal Calcium Sensor-1 Binds the D2 Dopamine Receptor and G-protein-coupled Receptor Kinase 1 (GRK1) Peptides Using Different Modes of Interactions</dcterms:title> <dcterms:rights rdf:resource="http://nbn-resolving.de/urn:nbn:de:bsz:352-20150914100631302-4485392-8"/> <dc:creator>Burgoyne, Robert D.</dc:creator> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/34939"/> <dc:creator>Lian, Lu-Yun</dc:creator> <dc:creator>Karuppiah, Vijaykumar</dc:creator> <dc:contributor>Pandalaneni, Sravan</dc:contributor> <dc:contributor>Haynes, Lee P.</dc:contributor> <dc:contributor>Derrick, Jeremy P.</dc:contributor> <dc:creator>Derrick, Jeremy P.</dc:creator> <dc:creator>Haynes, Lee P.</dc:creator> <dc:contributor>Burgoyne, Robert D.</dc:contributor> <dcterms:issued>2015-07-24</dcterms:issued> <dc:contributor>Saleem, Muhammad</dc:contributor> <dc:contributor>Karuppiah, Vijaykumar</dc:contributor> <dc:creator>Mayans, Olga</dc:creator> <dcterms:abstract xml:lang="eng">Neuronal calcium sensor-1 (NCS-1) is the primordial member of the neuronal calcium sensor family of EF-hand Ca(2+)-binding proteins. It interacts with both the G-protein-coupled receptor (GPCR) dopamine D2 receptor (D2R), regulating its internalization and surface expression, and the cognate kinases GRK1 and GRK2. Determination of the crystal structures of Ca(2+)/NCS-1 alone and in complex with peptides derived from D2R and GRK1 reveals that the differential recognition is facilitated by the conformational flexibility of the C-lobe-binding site. We find that two copies of the D2R peptide bind within the hydrophobic crevice on Ca(2+)/NCS-1, but only one copy of the GRK1 peptide binds. The different binding modes are made possible by the C-lobe-binding site of NCS-1, which adopts alternative conformations in each complex. C-terminal residues Ser-178-Val-190 act in concert with the flexible EF3/EF4 loop region to effectively form different peptide-binding sites. In the Ca(2+)/NCS-1·D2R peptide complex, the C-terminal region adopts a 310 helix-turn-310 helix, whereas in the GRK1 peptide complex it forms an α-helix. Removal of Ser-178-Val-190 generated a C-terminal truncation mutant that formed a dimer, indicating that the NCS-1 C-terminal region prevents NCS-1 oligomerization. We propose that the flexible nature of the C-terminal region is essential to allow it to modulate its protein-binding sites and adapt its conformation to accommodate both ligands. This appears to be driven by the variability of the conformation of the C-lobe-binding site, which has ramifications for the target specificity and diversity of NCS-1.</dcterms:abstract> <dc:language>eng</dc:language> <dc:creator>Saleem, Muhammad</dc:creator> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2016-08-04T13:35:45Z</dcterms:available> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2016-08-04T13:35:45Z</dc:date> <dc:contributor>Lian, Lu-Yun</dc:contributor> <dc:contributor>Mayans, Olga</dc:contributor> <dc:creator>Pandalaneni, Sravan</dc:creator> </rdf:Description> </rdf:RDF>

Dateiabrufe seit 04.08.2016 (Informationen über die Zugriffsstatistik)

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