Structural conservation predominates over sequence variability in the crown of HIV type 1's V3 loop.
The diversity of HIV-1 is a confounding problem for vaccine design, as the human immune response appears to favor poor or strain-specific responses to any given HIV-1 virus strain. A significant portion of this diversity is manifested as sequence variability in the loops of HIV-1's surface envelope glycoprotein. Here we show that the most variable sequence positions in the third variable (V3) loop crown cluster to a small zone on the surface of one face of the V3 loop ss-hairpin conformation. These results provide a novel visualization of the gp120 V3 loop, specifically demonstrating a surprising preponderance of conserved three-dimensional structure in a highly sequence-variable region. From a structural point of view, there appears to be less diversity in this region of the HIV-1 "principle neutralizing domain" than previously appreciated.
Almond
David
D
Department of Pharmacology, New York University School of Medicine (NYUSoM), New York, New York 10016, USA.
Kimura
Tetsuya
T
Kong
XiangPeng
X
Swetnam
James
J
Zolla-Pazner
Susan
S
Cardozo
Timothy
T
D017124:Conserved Sequence; D014644:Genetic Variation; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary
D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1