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.
Ding
Jianping
J
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.
Smith
Allen D
AD
Geisler
Sheila C
SC
Ma
Xuejun
X
Arnold
Gail Ferstandig
GF
Arnold
Eddy
E
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