Abstract
Cyanovirin (CV-N) is a small lectin with potent HIV neutralization activity, which could be exploited for a mucosal defense against HIV infection. The wild-type (wt) protein binds with high affinity to mannose-rich oligosaccharides on the surface of gp120 through two quasi-symmetric sites, located in domains A and B. We recently reported on a mutant of CV-N that contained a single functional mannose-binding site, domain B, showing that multivalent binding to oligomannosides is necessary for antiviral activity. The structure of the complex with dimannose determined at 1.8 Å resolution revealed a different conformation of the binding site than previously observed in the NMR structure of wt CV-N. Here, we present the 1.35 Å resolution structure of the complex, which traps three different binding conformations of the site and provides experimental support for a locking and gating mechanism in the nanoscale time regime observed by molecular dynamics simulations.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 939-944 |
| Number of pages | 6 |
| Journal | Protein Science |
| Volume | 17 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2008 |
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Keywords
- Antiviral protein
- Cyanovirin
- Lectins
- Sugar binding
- X-ray structure analysis
ASJC Scopus subject areas
- Biochemistry
Cite this
Conformational gating of dimannose binding to the antiviral protein cyanovirin revealed from the crystal structure at 1.35 Å resolution. / Fromme, Raimund; Katiliene, Zivile; Fromme, Petra; Ghirlanda, Giovanna.
In: Protein Science, Vol. 17, No. 5, 05.2008, p. 939-944.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Conformational gating of dimannose binding to the antiviral protein cyanovirin revealed from the crystal structure at 1.35 Å resolution
AU - Fromme, Raimund
AU - Katiliene, Zivile
AU - Fromme, Petra
AU - Ghirlanda, Giovanna
PY - 2008/5
Y1 - 2008/5
N2 - Cyanovirin (CV-N) is a small lectin with potent HIV neutralization activity, which could be exploited for a mucosal defense against HIV infection. The wild-type (wt) protein binds with high affinity to mannose-rich oligosaccharides on the surface of gp120 through two quasi-symmetric sites, located in domains A and B. We recently reported on a mutant of CV-N that contained a single functional mannose-binding site, domain B, showing that multivalent binding to oligomannosides is necessary for antiviral activity. The structure of the complex with dimannose determined at 1.8 Å resolution revealed a different conformation of the binding site than previously observed in the NMR structure of wt CV-N. Here, we present the 1.35 Å resolution structure of the complex, which traps three different binding conformations of the site and provides experimental support for a locking and gating mechanism in the nanoscale time regime observed by molecular dynamics simulations.
AB - Cyanovirin (CV-N) is a small lectin with potent HIV neutralization activity, which could be exploited for a mucosal defense against HIV infection. The wild-type (wt) protein binds with high affinity to mannose-rich oligosaccharides on the surface of gp120 through two quasi-symmetric sites, located in domains A and B. We recently reported on a mutant of CV-N that contained a single functional mannose-binding site, domain B, showing that multivalent binding to oligomannosides is necessary for antiviral activity. The structure of the complex with dimannose determined at 1.8 Å resolution revealed a different conformation of the binding site than previously observed in the NMR structure of wt CV-N. Here, we present the 1.35 Å resolution structure of the complex, which traps three different binding conformations of the site and provides experimental support for a locking and gating mechanism in the nanoscale time regime observed by molecular dynamics simulations.
KW - Antiviral protein
KW - Cyanovirin
KW - Lectins
KW - Sugar binding
KW - X-ray structure analysis
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UR - http://www.scopus.com/inward/citedby.url?scp=43049111403&partnerID=8YFLogxK
U2 - 10.1110/ps.083472808
DO - 10.1110/ps.083472808
M3 - Article
C2 - 18436959
AN - SCOPUS:43049111403
VL - 17
SP - 939
EP - 944
JO - Protein Science
JF - Protein Science
SN - 0961-8368
IS - 5
ER -