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| [[Image:2z21.jpg|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_2z21| PDB=2z21 | SCENE= }} | | {{STRUCTURE_2z21| PDB=2z21 | SCENE= }} |
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| '''Crystal Structure of a five site mutated Cyanovirin-N'''
| | ===Crystal Structure of a five site mutated Cyanovirin-N=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17636873}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17636873 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17636873}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Gp120]] | | [[Category: Gp120]] |
| [[Category: Sugar binding protein]] | | [[Category: Sugar binding protein]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 19:50:53 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 18:48:09 2008'' |
