Role for the disulfide-bonded region of human immunodeficiency virus type 1 gp41 in receptor-triggered activation of membrane fusion function.
The conserved disulfide-bonded region (DSR) of the human immunodeficiency virus type 1 (HIV-1) fusion glycoprotein, gp41, mediates association with the receptor-binding glycoprotein, gp120. Interactions between gp120, CD4 and chemokine receptors activate the fusion activity of gp41. The introduction of W596L and W610F mutations to the DSR of HIV-1(QH1549.13) blocked viral entry and hemifusion without affecting gp120-gp41 association. The fusion defect correlated with inhibition of CD4-triggered gp41 pre-hairpin formation, consistent with the DSR mutations having decoupled receptor-induced conformational changes in gp120 from gp41 activation. Our data implicate the DSR in sensing conformational changes in the gp120-gp41 complex that lead to fusion activation.
Macfarlane Burnet Institute for Medical Research and Public Health, Vic. 3004, Australia.
Anna K
AK
Bellamy-McIntyre
Séverine
S
Bär
Louise
L
Ludlow
Heidi E
HE
Drummer
Pantelis
P
Poumbourios
D019943:Amino Acid Substitution; D015704:CD4 Antigens / Q000378:metabolism*; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008561:Membrane Fusion; D009154:Mutation; D011487:Protein Conformation; D053586:Virus Internalization
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D003545:Cysteine