Linked Life Data

7778293

Source:http://linkedlifedata.com/resource/pubmed/id/7778293

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1995-7-11
pubmed:abstractText
The HIV-1-encoded Vpu protein induces a rapid and specific degradation of CD4 molecules in the endoplasmic reticulum (ER). In this study, Vpu-induced degradation of CD4 in the ER was investigated by quantitative immunoprecipitation of CD4 following cotransfection of COS-7 cells with CD4 and Vpu expressors in the presence of brefeldin A, a drug that blocks protein transport from the ER to the Golgi complex. In order to precisely define the sequence(s) or structural element(s) in the CD4 cytoplasmic domain necessary for Vpu-induced degradation, a panel of deletion and substitution mutants in the cytoplasmic domain of CD4 was generated and analyzed. In agreement with previous reports, our deletion analysis indicates that a region encompassing amino acids 411 to 419 (KRLLSEKKT) in the cytoplasmic domain of CD4 was required to confer Vpu sensitivity. However, six specific substitution mutations within this region did not confer CD4 resistance to Vpu, suggesting that neither the amino acid sequence nor the charge of the amino acids in this region was critical to Vpu-induced CD4 degradation. A dileucine motif that is important for internalization of CD4 and Nef-induced CD4 down-regulation was also not required for Vpu-induced CD4 degradation. Interestingly, two substitution mutants (CD4EMKL and CD4MK407,11PP) located in a more proximal cytoplasmic region of CD4 abolished Vpu-induced CD4 degradation. Computer-assisted analysis of the substitution and deletion mutants conferring CD4 resistance to Vpu-induced degradation indicated that these mutations disrupted a putative alpha-helix formed in the proximal cytoplasmic region of CD4. Taken together, these studies strongly suggest that a structural element in the proximal cytoplasmic region of CD4 contributes to Vpu sensitivity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0042-6822
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
209
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
615-23
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:7778293-Amino Acid Sequence, pubmed-meshheading:7778293-Animals, pubmed-meshheading:7778293-Antigens, CD, pubmed-meshheading:7778293-Antigens, CD4, pubmed-meshheading:7778293-Base Sequence, pubmed-meshheading:7778293-Brefeldin A, pubmed-meshheading:7778293-Cell Line, pubmed-meshheading:7778293-Cercopithecus aethiops, pubmed-meshheading:7778293-Cyclopentanes, pubmed-meshheading:7778293-DNA Primers, pubmed-meshheading:7778293-Endoplasmic Reticulum, pubmed-meshheading:7778293-Golgi Apparatus, pubmed-meshheading:7778293-HIV-1, pubmed-meshheading:7778293-Human Immunodeficiency Virus Proteins, pubmed-meshheading:7778293-Humans, pubmed-meshheading:7778293-Molecular Sequence Data, pubmed-meshheading:7778293-Polymerase Chain Reaction, pubmed-meshheading:7778293-Protein Processing, Post-Translational, pubmed-meshheading:7778293-Protein Structure, Secondary, pubmed-meshheading:7778293-Recombinant Proteins, pubmed-meshheading:7778293-Sequence Deletion, pubmed-meshheading:7778293-Substrate Specificity, pubmed-meshheading:7778293-Transfection, pubmed-meshheading:7778293-Viral Regulatory and Accessory Proteins
pubmed:year
1995
pubmed:articleTitle
Degradation of CD4 induced by human immunodeficiency virus type 1 Vpu protein: a predicted alpha-helix structure in the proximal cytoplasmic region of CD4 contributes to Vpu sensitivity.
pubmed:affiliation
Département de Microbiologie et Immunologie, Faculté de Médecine, Université de Montréal, Québec, Canada.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't