Linked Life Data

11772027

Source:http://linkedlifedata.com/resource/pubmed/id/11772027

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-1-4
pubmed:abstractText
Clusterin is the first identified extracellular mammalian chaperone and binds to a wide variety of partly unfolded, stressed proteins.Clusterin also binds to many different unstressed ligands including the cell surface receptor low-density lipoprotein receptor-related protein-2 (LRP-2). It is unknown whether clusterin binds to all of these many ligands via one or more binding sites. Furthermore, the region(s) of clusterin involved in these many binding interactions remain(s) to be identified. As part of an investigation of these issues, we expressed recombinant human clusterin in the yeast Pichia pastoris. The resultant protein had variable proteolytic truncations of the C-terminal region of the alpha-chain and the N-terminal region of the beta-chain. We compared the chaperone and ligand binding activities of this recombinant product with those of clusterin purified from human serum. We also tested whether the binding of clusterin to ligands could be inhibited by competitive binding with other clusterin ligands or by anti-clusterin monoclonal antibodies. Collectively, our results indicate that (i) clusterin has three independent classes of binding sites for LRP-2, stressed proteins, and unstressed ligands, respectively, and (ii) the binding sites for LRP-2 and stressed proteins are likely to be in parts of the molecule other than the C-terminal region of the alpha-chain or the N-terminal region of the beta-chain. It has been suggested that, in vivo, clusterin binds to toxic molecules in the extracellular environment and carries these to cells expressing LRP-2 for uptake and degradation. This hypothesis is supported by our demonstration that clusterin has discrete binding sites for LRP-2 and other (potentially toxic) molecules.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
282-91
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:11772027-Animals, pubmed-meshheading:11772027-Binding, Competitive, pubmed-meshheading:11772027-Binding Sites, pubmed-meshheading:11772027-Biotinylation, pubmed-meshheading:11772027-Cell Differentiation, pubmed-meshheading:11772027-Cells, Cultured, pubmed-meshheading:11772027-Clusterin, pubmed-meshheading:11772027-DNA Primers, pubmed-meshheading:11772027-Electrophoresis, Gel, Two-Dimensional, pubmed-meshheading:11772027-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:11772027-Glutathione Transferase, pubmed-meshheading:11772027-Glycoproteins, pubmed-meshheading:11772027-Humans, pubmed-meshheading:11772027-Ligands, pubmed-meshheading:11772027-Low Density Lipoprotein Receptor-Related Protein-2, pubmed-meshheading:11772027-Mice, pubmed-meshheading:11772027-Molecular Chaperones, pubmed-meshheading:11772027-Pichia, pubmed-meshheading:11772027-Polymerase Chain Reaction, pubmed-meshheading:11772027-Recombinant Fusion Proteins, pubmed-meshheading:11772027-Synaptic Membranes
pubmed:year
2002
pubmed:articleTitle
Evidence that clusterin has discrete chaperone and ligand binding sites.
pubmed:affiliation
Institute for Medicine and Engineering, University of Pennsylvania, 1170 Vagelos Research Labs, 3340 Smith Walk, Philadelphia, Pennsylvania 19104-6383, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't