A twin-cysteine motif in the V2 region of gp120 is associated with SIV envelope trimer stabilization.
The V1 and V2 variable regions of the primate immunodeficiency viruses contribute to the trimer association domain of the gp120 exterior envelope glycoprotein. A pair of V2 cysteine residues at 183 and 191 ("twin cysteines") is present in several simian immunodeficiency viruses, human immunodeficiency virus type 2 (HIV-2) and some SIV(cpz) lineages, but not in HIV-1. To examine the role of this potentially disulfide-bonded twin-cysteine motif, the cysteine residues in the SIVmac239 envelope glycoproteins were individually and pairwise substituted by alanine residues. All of the twin-cysteine mutants exhibited decreases in gp120 association with the Env trimer, membrane-fusing activity, and ability to support virus entry. Thus, the twin-cysteine motif plays a role in Env trimer stabilization in SIV and may do so in HIV-2 and some SIV(cpz) as well. This implies that HIV-1 lost the twin-cysteines, and may have relatively unstable Env trimers compared to SIV and HIV-2.
Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
Christopher
C
Bohl
Dane
D
Bowder
Jesse
J
Thompson
Levon
L
Abrahamyan
Sandra
S
Gonzalez-Ramirez
Youdong
Y
Mao
Joseph
J
Sodroski
Charles
C
Wood
Shi-hua
SH
Xiang
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002459:Cell Fusion; D002460:Cell Line; D003545:Cysteine / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D010802:Phylogeny; D055503:Protein Multimerization; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000378:metabolism* / Q000472:pathogenicity; D013329:Structure-Activity Relationship; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism*
D008562:Membrane Glycoproteins; D050505:Mutant Proteins; D021122:Protein Subunits; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus; D003545:Cysteine