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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2005-3-14
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pubmed:abstractText |
RS1, also known as retinoschisin, is an extracellular protein that plays a crucial role in the cellular organization of the retina. Mutations in RS1 are responsible for X-linked retinoschisis, a common, early-onset macular degeneration in males that results in a splitting of the inner layers of the retina and severe loss in vision. RS1 is assembled and secreted from photoreceptors and bipolar cells as a homo-oligomeric protein complex. Each subunit consists of a 157-amino acid discoidin domain flanked by two small segments of 39 and 5 amino acids. To begin to understand how the structure of RS1 relates to its role in retinal cell adhesion and X-linked retinoschisis, we have determined the subunit organization and disulfide bonding pattern of RS1 by SDS gel electrophoresis, velocity sedimentation, and mass spectrometry. Our results indicate that RS1 exists as a novel octamer in which the eight subunits are joined together by Cys(59)-Cys(223) intermolecular disulfide bonds. Subunits within the octamer are further organized into dimers mediated by Cys(40)-Cys(40) bonds. These cysteines lie just outside the discoidin domain indicating that these flanking segments primarily function in the octamerization of RS1. Within the discoidin domain, two cysteine pairs (Cys(63)-Cys(219) and Cys(110)-Cys(142)) form intramolecular disulfide bonds that are important in protein folding, and one cysteine (Cys(83)) exists in its reduced state. Because mutations that disrupt subunit assembly cause X-linked retinoschisis, the assembly of RS1 into a disulfide-linked homo-octamer appears to be critical for its function as a retinal cell adhesion protein.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Ammonium Sulfate,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Detergents,
http://linkedlifedata.com/resource/pubmed/chemical/Disulfides,
http://linkedlifedata.com/resource/pubmed/chemical/Eye Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/RS1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Mitogen,
http://linkedlifedata.com/resource/pubmed/chemical/Trypsin,
http://linkedlifedata.com/resource/pubmed/chemical/discoidin receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10721-30
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15644328-Amino Acid Sequence,
pubmed-meshheading:15644328-Ammonium Sulfate,
pubmed-meshheading:15644328-Animals,
pubmed-meshheading:15644328-Blotting, Western,
pubmed-meshheading:15644328-Cattle,
pubmed-meshheading:15644328-Cell Adhesion,
pubmed-meshheading:15644328-Cell Line,
pubmed-meshheading:15644328-Chromosomes, Human, X,
pubmed-meshheading:15644328-Cysteine,
pubmed-meshheading:15644328-DNA, Complementary,
pubmed-meshheading:15644328-Detergents,
pubmed-meshheading:15644328-Dimerization,
pubmed-meshheading:15644328-Disulfides,
pubmed-meshheading:15644328-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:15644328-Eye Proteins,
pubmed-meshheading:15644328-Humans,
pubmed-meshheading:15644328-Immunoprecipitation,
pubmed-meshheading:15644328-Mass Spectrometry,
pubmed-meshheading:15644328-Models, Biological,
pubmed-meshheading:15644328-Molecular Sequence Data,
pubmed-meshheading:15644328-Mutation,
pubmed-meshheading:15644328-Peptide Mapping,
pubmed-meshheading:15644328-Peptides,
pubmed-meshheading:15644328-Protein Binding,
pubmed-meshheading:15644328-Protein Conformation,
pubmed-meshheading:15644328-Protein Folding,
pubmed-meshheading:15644328-Protein Structure, Tertiary,
pubmed-meshheading:15644328-Protein Transport,
pubmed-meshheading:15644328-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:15644328-Receptors, Mitogen,
pubmed-meshheading:15644328-Retina,
pubmed-meshheading:15644328-Retinoschisis,
pubmed-meshheading:15644328-Trypsin
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pubmed:year |
2005
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pubmed:articleTitle |
RS1, a discoidin domain-containing retinal cell adhesion protein associated with X-linked retinoschisis, exists as a novel disulfide-linked octamer.
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pubmed:affiliation |
Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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