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Conformational gating of dimannose binding to the antiviral protein cyanovirin revealed from the crystal structure at 1.35 Å resolution
Author(s) -
Fromme Raimund,
Katiliene Zivile,
Fromme Petra,
Ghirlanda Giovanna
Publication year - 2008
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.083472808
Subject(s) - chemistry , binding site , lectin , gating , mutant , biophysics , protein structure , mannose , antiviral protein , stereochemistry , crystallography , biochemistry , biology , gene , rna
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.