| Structural highlights
2z21 is a 2 chain structure with sequence from Nostoc ellipsosporum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | 2pys, 1lom, 1m5m, 2ezm, 1iiy, 1l5e |
| Gene: | Cyanovirin-N (Nostoc ellipsosporum) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Cyanovirin-N (CV-N) is a 101 amino acid cyanobacterial lectin with potent antiviral activity against HIV, mediated by high-affinity binding to branched N-linked oligomannosides on the viral surface envelope protein gp120. The protein contains two carbohydrate-binding domains, A and B, each of which binds short oligomannosides independently in vitro. The interaction to gp120 could involve either a single domain or both domains simultaneously; it is not clear which mode would elicit the antiviral activity. The model is complicated by the formation of a domain-swapped dimer form, in which part of each domain is exchanged between two monomers, which contains four functional carbohydrate-binding domains. To clarify whether multivalent interactions with gp120 are necessary for the antiviral activity, we engineered a novel mutant, P51G-m4-CVN, in which the binding site on domain A has been knocked out; in addition, a [P51G] mutation prevents the formation of domain-swapped dimers under physiological conditions. Here, we present the crystal structures at 1.8 A of the free and of the dimannose-bound forms of P51G-m4-CVN, revealing a monomeric structure in which only domain B is bound to dimannose. P51G-m4-CVN binds gp120 with an affinity almost 2 orders of magnitude lower than wt CV-N and is completely inactive against HIV. The tight binding to gp120 is recovered in the domain-swapped version of P51G-m4-CVN, prepared under extreme conditions. Our findings show that the presence of at least two oligomannoside-binding sites, either by the presence of intact domains A and B or by formation of domain-swapped dimers, is essential for activity.
A monovalent mutant of cyanovirin-N provides insight into the role of multiple interactions with gp120 for antiviral activity.,Fromme R, Katiliene Z, Giomarelli B, Bogani F, Mc Mahon J, Mori T, Fromme P, Ghirlanda G Biochemistry. 2007 Aug 14;46(32):9199-207. Epub 2007 Jul 18. PMID:17636873[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fromme R, Katiliene Z, Giomarelli B, Bogani F, Mc Mahon J, Mori T, Fromme P, Ghirlanda G. A monovalent mutant of cyanovirin-N provides insight into the role of multiple interactions with gp120 for antiviral activity. Biochemistry. 2007 Aug 14;46(32):9199-207. Epub 2007 Jul 18. PMID:17636873 doi:10.1021/bi700666m
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