Linked Life Data

18590740

Source:http://linkedlifedata.com/resource/pubmed/id/18590740

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-8-11
pubmed:databankReference
pubmed:abstractText
Suppressor of cytokine signalling 3 (SOCS3) is responsible for regulating the cellular response to a variety of cytokines, including interleukin 6 and leukaemia inhibitory factor. Identification of the SOCS box domain led to the hypothesis that SOCS3 can associate with functional E3 ubiquitin ligases and thereby induce the degradation of bound signalling proteins. This model relies upon an interaction between the SOCS box, elonginBC and a cullin protein that forms the E3 ligase scaffold. We have investigated this interaction in vitro using purified components and show that SOCS3 binds to elonginBC and cullin5 with high affinity. The SOCS3-elonginBC interaction was further characterised by determining the solution structure of the SOCS box-elonginBC ternary complex and by deletion and alanine scanning mutagenesis of the SOCS box. These studies revealed that conformational flexibility is a key feature of the SOCS-elonginBC interaction. In particular, the SOCS box is disordered in isolation and only becomes structured upon elonginBC association. The interaction depends upon the first 12 residues of the SOCS box domain and particularly on a deeply buried, conserved leucine. The SOCS box, when bound to elonginBC, binds tightly to cullin5 with 100 nM affinity. Domains upstream of the SOCS box are not required for elonginBC or cullin5 association, indicating that the SOCS box acts as an independent binding domain capable of recruiting elonginBC and cullin5 to promote E3 ligase formation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1089-8638
pubmed:author
pubmed:issnType
Electronic
pubmed:day
12
pubmed:volume
381
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
928-40
pubmed:meshHeading
pubmed-meshheading:18590740-Alanine, pubmed-meshheading:18590740-Amino Acid Sequence, pubmed-meshheading:18590740-Animals, pubmed-meshheading:18590740-Binding Sites, pubmed-meshheading:18590740-Calorimetry, pubmed-meshheading:18590740-Cullin Proteins, pubmed-meshheading:18590740-Epitopes, pubmed-meshheading:18590740-Magnetic Resonance Spectroscopy, pubmed-meshheading:18590740-Mice, pubmed-meshheading:18590740-Models, Molecular, pubmed-meshheading:18590740-Molecular Sequence Data, pubmed-meshheading:18590740-Mutagenesis, pubmed-meshheading:18590740-Mutant Proteins, pubmed-meshheading:18590740-Protein Binding, pubmed-meshheading:18590740-Suppressor of Cytokine Signaling Proteins, pubmed-meshheading:18590740-Transcription Factors, pubmed-meshheading:18590740-Ubiquitin-Protein Ligases, pubmed-meshheading:18590740-Ultracentrifugation, pubmed-meshheading:18590740-src Homology Domains
pubmed:year
2008
pubmed:articleTitle
The SOCS box domain of SOCS3: structure and interaction with the elonginBC-cullin5 ubiquitin ligase.
pubmed:affiliation
Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia. babon@wehi.edu.au
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural