Source:http://linkedlifedata.com/resource/pubmed/id/17020884
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
48
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pubmed:dateCreated |
2006-11-27
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pubmed:databankReference | |
pubmed:abstractText |
Recoverin, a member of the neuronal calcium sensor branch of the EF-hand superfamily, serves as a calcium sensor that regulates rhodopsin kinase (RK) activity in retinal rod cells. We report here the NMR structure of Ca(2+)-bound recoverin bound to a functional N-terminal fragment of rhodopsin kinase (residues 1-25, called RK25). The overall main-chain structure of recoverin in the complex is similar to structures of Ca(2+)-bound recoverin in the absence of target (<1.8A root-mean-square deviation). The first eight residues of recoverin at the N terminus are solvent-exposed, enabling the N-terminal myristoyl group to interact with target membranes, and Ca(2+) is bound at the second and third EF-hands of the protein. RK25 in the complex forms an amphipathic helix (residues 4-16). The hydrophobic face of the RK25 helix (Val-9, Val-10, Ala-11, Ala-14, and Phe-15) interacts with an exposed hydrophobic groove on the surface of recoverin lined by side-chain atoms of Trp-31, Phe-35, Phe-49, Ile-52, Tyr-53, Phe-56, Phe-57, Tyr-86, and Leu-90. Residues of recoverin that contact RK25 are highly conserved, suggesting a similar target binding site structure in all neuronal calcium sensor proteins. Site-specific mutagenesis and deletion analysis confirm that the hydrophobic residues at the interface are necessary and sufficient for binding. The recoverin-RK25 complex exhibits Ca(2+)-induced binding to rhodopsin immobilized on concanavalin-A resin. We propose that Ca(2+)-bound recoverin is bound between rhodopsin and RK in a ternary complex on rod outer segment disk membranes, thereby blocking RK interaction with rhodopsin at high Ca(2+).
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
281
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
37237-45
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:17020884-Amino Acid Sequence,
pubmed-meshheading:17020884-Animals,
pubmed-meshheading:17020884-Binding Sites,
pubmed-meshheading:17020884-Calcium,
pubmed-meshheading:17020884-Cattle,
pubmed-meshheading:17020884-Crystallography, X-Ray,
pubmed-meshheading:17020884-Dose-Response Relationship, Drug,
pubmed-meshheading:17020884-G-Protein-Coupled Receptor Kinase 1,
pubmed-meshheading:17020884-Magnetic Resonance Spectroscopy,
pubmed-meshheading:17020884-Molecular Conformation,
pubmed-meshheading:17020884-Molecular Sequence Data,
pubmed-meshheading:17020884-Mutagenesis, Site-Directed,
pubmed-meshheading:17020884-Neurons,
pubmed-meshheading:17020884-Protein Binding,
pubmed-meshheading:17020884-Recoverin,
pubmed-meshheading:17020884-Rhodopsin
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pubmed:year |
2006
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pubmed:articleTitle |
Structural basis for calcium-induced inhibition of rhodopsin kinase by recoverin.
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pubmed:affiliation |
Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850, USA. ames@chem.ucdavis.edu
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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