Conformational gating of dimannose binding to the antiviral protein cyanovirin revealed from the crystal structure at 1.35 Å resolution

Raimund Fromme, Zivile Katiliene, Petra Fromme, Giovanna Ghirlanda

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19 Citations (Scopus)

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 languageEnglish
Pages (from-to)939-944
Number of pages6
JournalProtein Science
Volume17
Issue number5
DOIs
Publication statusPublished - May 1 2008

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Keywords

  • Antiviral protein
  • Cyanovirin
  • Lectins
  • Sugar binding
  • X-ray structure analysis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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