Document 0603
 DOCN  M9550603
 TI    The human immunodeficiency virus type 1 Vpu protein specifically binds
       to the cytoplasmic domain of CD4: implications for the mechanism of
       degradation.
 DT    9505
 AU    Bour S; Schubert U; Strebel K; Laboratory of Molecular Microbiology,
       National Institute of; Allergy and Infectious Diseases.
 SO    J Virol. 1995 Mar;69(3):1510-20. Unique Identifier : AIDSLINE
       MED/95156576
 AB    We have recently demonstrated that coexpression of Vpu and CD4 in HeLa
       cells results in the degradation of CD4 in the endoplasmic reticulum.
       The sensitivity of CD4 to Vpu-mediated degradation is conferred by the
       presence of specific sequences located between amino acids 402 and 420
       in the CD4 cytoplasmic domain. Using an in vitro translation system, we
       also showed that degradation of CD4 by Vpu requires the two proteins to
       be present in the same membrane compartment. Although these results
       suggest that spatial proximity between CD4 and Vpu may be critical in
       triggering degradation, it remains unknown whether the two molecules
       have the ability to interact with each other. In order to better define
       the mechanisms involved in CD4 degradation, we investigated the
       existence and functional relevance of direct interactions between CD4
       and Vpu. Coimmunoprecipitation experiments showed that Vpu specifically
       binds to the cytoplasmic tail of CD4. This phenomenon is relevant to the
       mechanism of CD4 degradation since the ability of CD8/CD4 chimeric
       molecules and various CD4 mutants to form complexes with Vpu correlates
       with their sensitivity to degradation. Accordingly, we found that amino
       acid residues in the CD4 cytoplasmic tail previously shown to be
       important for degradation are necessary for Vpu binding. We further
       demonstrate that a deletion mutant of Vpu as well as a phosphorylation
       mutant, both biologically inactive with regard to CD4 degradation,
       retained the capacity to interact with the CD4 cytoplasmic domain. Taken
       together, these results indicate that Vpu binding is necessary to
       trigger CD4 degradation. However, the binding to target molecules is not
       sufficient per se to cause degradation. Interaction between CD4 and Vpu
       is thus likely to be an early event critical in triggering a multistep
       process leading to CD4 degradation.
 DE    Amino Acid Sequence  Antigens, CD4/*METABOLISM  Chimeric
       Proteins/METABOLISM  Cytoplasm/METABOLISM  Endoplasmic
       Reticulum/METABOLISM  Gene Products, vpu/*METABOLISM  Hela Cells  Human
       HIV-1/*METABOLISM  In Vitro  Molecular Sequence Data  Phosphorylation
       Protein Binding  Recombinant Proteins  Structure-Activity Relationship
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).