Crystal structure of a human rhinovirus that displays part of the HIV-1 V3 loop and induces neutralizing antibodies against HIV-1.
We report the 2.7 A resolution structure of a chimeric rhinovirus, MN-III-2, that displays part of the HIV-1 gp120 V3 loop and elicits HIV-neutralizing antibodies. The V3 loop insert is dominated by two type I beta turns. The structures of two adjacent tripeptides resemble those of analogous segments in three Fab/V3 loop peptide complexes. Although two of the three corresponding antibodies bind and neutralize MN-III-2 well, only one of the three can bind without significant rearrangement. These results suggest that the V3 loop insert: (1) can share some local conformational similarity to V3 loop sequences presented on different structural frameworks; (2) must be able to adopt multiple conformations, even in a relatively constrained environment; and (3) may mimic the conformational variability of the epitope on HIV-1, increasing the likelihood of eliciting appropriate neutralizing immune responses.
Center for Advanced Biotechnology and Medicine (CABM) and Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 679 Hoes Lane, Piscataway 08854, USA.
Jianping
J
Ding
Allen D
AD
Smith
Sheila C
SC
Geisler
Xuejun
X
Ma
Gail Ferstandig
GF
Arnold
Eddy
E
Arnold
D018360:Crystallography, X-Ray; D015483:HIV Antibodies / Q000737:chemistry*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D012229:Rhinovirus / Q000737:chemistry* / Q000235:genetics; D013110:Sphingosine / Q000737:chemistry
D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D013110:Sphingosine