Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin

Yinan Liu, Jacob R. Carroll, Lindsey A. Holt, James McMahon, Barbara Giomarelli, Giovanna Ghirlanda

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Cyanovirin-N (CV-N) is a cyanobacterial lectin that binds to specific oligomannoses on the surface of gp120, resulting in nanomolar antiviral activity against HIV. In its monomeric form, CV-N contains two functional carbohydrate-binding domains, A and B. When refolded at high concentration, the protein can form a domain-swapped dimer. To clarify the role of multiple-binding sites in CV-N, we previously designed a monomeric mutant, P51G-m4-CVN, in which the binding site on domain A was rendered ineffective by four mutations (m4); in addition, a hinge region mutation (P51G) hinders the formation of a domain swapped dimer. The protein bound gp120 with diminished affinity and was completely inactive against HIV. Here, we present two mutants, ΔQ50-m4-CVN and S52P-m4-CVN, which fold exclusively as domain-swapped dimers while containing the four mutations that abolish domain A. The dimers contain two intact B domains, thus restoring multivalency. ΔQ50-m4-CVN and S52P-m4-CVN bind gp120 at low-nanomolar concentrations and recover in part the antiviral activity of wt CV-N. These results indicate that the number of carbohydrate binding domains, rather than their identity, is crucial to CV-N functionality.

Original languageEnglish
Pages (from-to)194-200
Number of pages7
JournalBiopolymers
Volume92
Issue number3
DOIs
Publication statusPublished - Aug 3 2009

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Keywords

  • Antiviral protein
  • Cyanovirin
  • HIV
  • Lectin
  • Multivalency

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry

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