Linked Life Data

9454695

Source:http://linkedlifedata.com/resource/pubmed/id/9454695

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-2-20
pubmed:abstractText
Previous studies have shown that human papillomavirus (HPV) E4 proteins undergo oligomerisation, although the precise sequences involved have not been identified. Using the yeast two-hybrid system we have identified HPV 1 E4 sequences that are critical to multimerisation. Fusion proteins were created by linking wild-type and mutant E4 proteins to a LexA DNA-binding domain or a B42 transactivation domain. HPV 1 E4:E4 interactions were examined by expression of these fusion proteins in Saccharomyces cerevisiae. This assay showed that (1) amino acid residues 95 to 115 at the carboxy-terminus were critical for oligomerisation and (2) hydrophobic residues (isoleucine 107, phenylalanine 114) in this domain are major determinants in the formation of oligomers. Interestingly, the carboxy-terminal domain shares homology with other E4 proteins of cutaneous HPV types and, furthermore, positions 107 and 114 are conserved residues. Substitution of the conserved aspartate amino acids (residues 110 and 112) did not abrogate E4 oligomerisation. Chemical cross-linking of wart and recombinant (baculovirus-expressed) HPV 1 E4 protein indicated that in solution this viral protein forms complexes consistent in size with either trimers or tetramers. These complexes were resistant to urea denaturation and are not dependent on the formation of disulphide linkages. A mutant protein containing a deletion of residues 110 to 115 was unable to form oligomers following cross-linking supporting a role for this region in mediating E4:E4 interactions. We conclude that oligomerisation of the HPV 1 E4 protein is likely to be mediated by carboxy-terminal residues and that conserved hydrophobic residues of this domain play a major role in E4 oligomerisation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0042-6822
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
240
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
221-31
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Identification of conserved hydrophobic C-terminal residues of the human papillomavirus type 1 E1E4 protein necessary for E4 oligomerisation in vivo.
pubmed:affiliation
Cancer Research Campaign Institute for Cancer Studies, Medical School, University of Birmingham, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't