Structure and Glycan Binding of a New Cyanovirin-N Homolog

• DOI: 10.1074/jbc.m116.740415
• Publication Date: 2016-07-12T01:07:49Z
• Authors: Elena Matei; Rohan Basu; William Furey; Jiong Shi; Conor Calnan; Christopher Aiken; Angela M. Gronenborn
• Keywords: Male; 0301 basic medicine; HIV Infections; HIV Envelope Protein gp120; Crystallography, X-Ray; Cell Line; 3. Good health; 03 medical and health sciences; Mannose-Binding Lectins; Bacterial Proteins; Structural Homology, Protein; HIV-1; Humans; Cyanothece; Carrier Proteins; Mannose; Protein Binding

The HIV-1 envelope glycoprotein gp120 is heavily glycosylated and bears numerous high mannose sugars. These sugars can serve as targets for HIV-inactivating compounds, such as antibodies and lectins, which bind to the glycans and interfere with viral entry into the target cell. We determined the 1.6 Å x-ray structure of Cyt-CVNH, a recently identified lectin from the cyanobacterium Cyanothece(7424), and elucidated its glycan specificity by NMR. The Cyt-CVNH structure and glycan recognition profile are similar to those of other CVNH proteins, with each domain specifically binding to Manα(1-2)Manα units on the D1 and D3 arms of high mannose glycans. However, in contrast to CV-N, no cross-linking and precipitation of the cross-linked species in solution was observed upon Man-9 binding, allowing, for the first time, investigation of the interaction of Man-9 with a member of the CVNH family by NMR. HIV assays showed that Cyt-CVNH is able to inhibit HIV-1 with ∼4-fold higher potency than CV-N(P51G), a stabilized version of wild type CV-N. Therefore, Cyt-CVNH may qualify as a valuable lectin for potential microbicidal use.