Conserved structural elements in the V3 crown of HIV-1 gp120.
Binding of the third variable region (V3) of the HIV-1 envelope glycoprotein gp120 to the cell-surface coreceptors CCR5 or CXCR4 during viral entry suggests that there are conserved structural elements in this sequence-variable region. These conserved elements could serve as epitopes to be targeted by a vaccine against HIV-1. Here we perform a systematic structural analysis of representative human anti-V3 monoclonal antibodies in complex with V3 peptides, revealing that the crown of V3 has four conserved structural elements: an arch, a band, a hydrophobic core and the peptide backbone. These are either unaffected by or are subject to minimal sequence variation. As these regions are targeted by cross-clade neutralizing human antibodies, they provide a blueprint for the design of vaccine immunogens that could elicit broadly cross-reactive protective antibodies.
Jiang
Xunqing
X
Department of Biochemistry, New York University School of Medicine, New York, New York, USA.
Burke
Valicia
V
Totrov
Maxim
M
Williams
Constance
C
Cardozo
Timothy
T
Gorny
Miroslaw K
MK
Zolla-Pazner
Susan
S
Kong
Xiang-Peng
XP
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007128:Immunoglobulin Fragments / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D007128:Immunoglobulin Fragments; D010455:Peptides