Linked Life Data

10692452

Source:http://linkedlifedata.com/resource/pubmed/id/10692452

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2000-4-3
pubmed:databankReference
pubmed:abstractText
Epsin is a recently identified protein that appears to play an important role in clathrin-mediated endocytosis. The central region of epsin 1, the so-called DPW domain, binds to the heterotetrameric AP-2 adaptor complex by associating directly with the globular appendage of the alpha subunit. We have found that this central portion of epsin 1 also associates with clathrin. The interaction with clathrin is direct and not mediated by epsin-bound AP-2. Alanine scanning mutagenesis shows that clathrin binding depends on the sequence (257)LMDLADV located within the epsin 1 DPW domain. This sequence, related to the known clathrin-binding sequences in the adaptor beta subunits, amphiphysin, and beta-arrestin, facilitates the association of epsin 1 with the terminal domain of the clathrin heavy chain. Unexpectedly, inhibiting the binding of AP-2 to the GST-epsin DPW fusion protein by progressively deleting DPW triplets but leaving the LMDLADV sequence intact, diminishes the association of clathrin in parallel with AP-2. Because the beta subunit of the AP-2 complex also contains a clathrin-binding site, optimal association with soluble clathrin appears to depend on the presence of at least two distinct clathrin-binding sites, and we show that a second clathrin-binding sequence (480)LVDLD, located within the carboxyl-terminal segment of epsin 1, also interacts with clathrin directly. The LMDLADV and LVDLD sequences act cooperatively in clathrin recruitment assays, suggesting that they bind to different sites on the clathrin-terminal domain. The evolutionary conservation of similar clathrin-binding sequences in several metazoan epsin-like molecules suggests that the ability to establish multiple protein-protein contacts within a developing clathrin-coated bud is an important aspect of epsin function.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6479-89
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10692452-Adaptor Protein Complex alpha Subunits, pubmed-meshheading:10692452-Adaptor Proteins, Vesicular Transport, pubmed-meshheading:10692452-Amino Acid Sequence, pubmed-meshheading:10692452-Animals, pubmed-meshheading:10692452-Binding Sites, pubmed-meshheading:10692452-Carrier Proteins, pubmed-meshheading:10692452-Cells, Cultured, pubmed-meshheading:10692452-Clathrin, pubmed-meshheading:10692452-Endocytosis, pubmed-meshheading:10692452-Evolution, Molecular, pubmed-meshheading:10692452-Fluorescent Antibody Technique, pubmed-meshheading:10692452-Kidney, pubmed-meshheading:10692452-Membrane Proteins, pubmed-meshheading:10692452-Molecular Sequence Data, pubmed-meshheading:10692452-Mutagenesis, pubmed-meshheading:10692452-Neuropeptides, pubmed-meshheading:10692452-Protein Binding, pubmed-meshheading:10692452-Rats, pubmed-meshheading:10692452-Recombinant Fusion Proteins, pubmed-meshheading:10692452-Vesicular Transport Proteins
pubmed:year
2000
pubmed:articleTitle
Epsin binds to clathrin by associating directly with the clathrin-terminal domain. Evidence for cooperative binding through two discrete sites.
pubmed:affiliation
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't