Format

Send to

Choose Destination
Biopolymers. 2009;92(3):194-200. doi: 10.1002/bip.21173.

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

Author information

1
Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287-1604, USA.

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, DeltaQ50-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. DeltaQ50-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.

PMID:
19235857
DOI:
10.1002/bip.21173
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center