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

19 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 (US)
Pages (from-to)194-200
Number of pages7
JournalBiopolymers
Volume92
Issue number3
DOIs
StatePublished - 2009

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Dimers
HIV
Binding sites
Carbohydrates
Mutation
Antiviral Agents
Binding Sites
Proteins
Hinges
Lectins
cyanovirin N

Keywords

  • Antiviral protein
  • Cyanovirin
  • HIV
  • Lectin
  • Multivalency

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Biomaterials
  • Organic Chemistry

Cite this

Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. / Liu, Yinan; Carroll, Jacob R.; Holt, Lindsey A.; McMahon, James; Giomarelli, Barbara; Ghirlanda, Giovanna.

In: Biopolymers, Vol. 92, No. 3, 2009, p. 194-200.

Research output: Contribution to journalArticle

Liu, Y, Carroll, JR, Holt, LA, McMahon, J, Giomarelli, B & Ghirlanda, G 2009, 'Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin', Biopolymers, vol. 92, no. 3, pp. 194-200. https://doi.org/10.1002/bip.21173
Liu, Yinan ; Carroll, Jacob R. ; Holt, Lindsey A. ; McMahon, James ; Giomarelli, Barbara ; Ghirlanda, Giovanna. / Multivalent interactions with gp120 are required for the anti-HIV activity of Cyanovirin. In: Biopolymers. 2009 ; Vol. 92, No. 3. pp. 194-200.
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