Stimulation of heterologous protein degradation by the Vpu protein of HIV-1 requires the transmembrane and cytoplasmic domains of CD4.
The small membrane protein Vpu of human immunodeficiency virus type 1 stimulates rapid degradation of CD4 molecules that are retained in the endoplasmic reticulum. To analyze the domain(s) of CD4 involved in Vpu-stimulated degradation, we examined degradation of hybrid proteins made between the vesicular stomatitis virus glycoprotein (VSV G) and CD4. Vpu expression stimulated rapid degradation of a hybrid consisting of the extracellular domain of VSV G linked to the transmembrane and cytoplasmic domains of CD4. Analysis of additional hybrids showed that both the cytoplasmic and transmembrane domains of CD4 were required for this Vpu-stimulated degradation. This conclusion is in apparent conflict with a recent study showing that the cytoplasmic domain of CD4 alone is sufficient to cause Vpu-stimulated degradation of a CD8-CD4 hybrid protein. The apparent conflict may be explained by the presence of related sequences or structures in the transmembrane domains of CD4 and CD8 that are involved in binding Vpu directly or that interact with the Vpu-stimulated degradation system.
Buonocore
L
L
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510.
Turi
T G
TG
Crise
B
B
Rose
J K
JK
D000595:Amino Acid Sequence; D001483:Base Sequence; D015704:CD4 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000235:genetics; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D000086082:Viroporin Proteins
D015704:CD4 Antigens; D006023:Glycoproteins; D054298:Human Immunodeficiency Virus Proteins; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D054334:Viral Regulatory and Accessory Proteins; C028391:G protein, vesicular stomatitis virus; C076613:recombinant soluble CD4; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins