Structure of a V3-containing HIV-1 gp120 core.
The third variable region (V3) of the HIV-1 gp120 envelope glycoprotein is immunodominant and contains features essential for coreceptor binding. We determined the structure of V3 in the context of an HIV-1 gp120 core complexed to the CD4 receptor and to the X5 antibody at 3.5 angstrom resolution. Binding of gp120 to cell-surface CD4 would position V3 so that its coreceptor-binding tip protrudes 30 angstroms from the core toward the target cell membrane. The extended nature and antibody accessibility of V3 explain its immunodominance. Together, the results provide a structural rationale for the role of V3 in HIV entry and neutralization.
Huang
Chih-chin
CC
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Tang
Min
M
Zhang
Mei-Yun
MY
Majeed
Shahzad
S
Montabana
Elizabeth
E
Stanfield
Robyn L
RL
Dimitrov
Dimiter S
DS
Korber
Bette
B
Sodroski
Joseph
J
Wilson
Ian A
IA
Wyatt
Richard
R
Kwong
Peter D
PD
D000595:Amino Acid Sequence; D001665:Binding Sites; D015704:CD4 Antigens / Q000737:chemistry / Q000378:metabolism*; D003460:Crystallization; D018360:Crystallography, X-Ray; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D016056:Immunodominant Epitopes; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D019713:Receptors, CCR5 / Q000737:chemistry / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000737:chemistry / Q000378:metabolism
D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D019713:Receptors, CCR5; D019718:Receptors, CXCR4