Jayaprakash, NG and Singh, A and Vivek, R and Yadav , S and Pathak , P and Trivedi, J and Jayaraman , N and Nandi , D and Mitra , D and Surolia, A (2020) The barley lectin, Horcolin binds high mannoseglycans in a multivalent fashion, enabling high affinity, specific inhibition ofcellular HIV infection. Journal of Biological Chemistry, 295 (34). pp. 12111-12129.

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Abstract

N-Linked glycans are critical to the infection cycle of HIV, and most neutralizing antibodies target the high-mannose glycans found on the surface envelope glycoprotein-120 (gp120). Carbohydrate-binding proteins, particularly mannose-binding lectins, have also been shown to bind these glycans. Despite their therapeutic potency, their ability to cause lymphocyte proliferation limits their application. In this study, we report one such lectin named horcolin (Hordeum vulgare lectin), seen to lack mitogenicity owing to the divergence in the residues at its carbohydrate-binding sites, which makes it a promising candidate for exploration as an anti-HIV agent. Extensive isothermal titration calorimetry experiments reveal that the lectin was sensitive to the length and branching of mannooligosaccharides and thereby the total valency. Modeling and simulation studies demonstrate two distinct modes of binding, a monovalent binding to shorter saccharides and a bivalent mode for higher glycans, involving simultaneous interactions of multiple glycan arms with the primary carbohydrate-binding sites. This multivalent mode of binding was further strengthened by interactions of core mannosyl residues with a secondary conserved site on the protein, leading to an exponential increase in affinity. Finally, we confirmed the interaction of horcolin with recombinant gp120 and gp140 with high affinity and inhibition of HIV infection at nanomolar concentrations without mitogenicity.

Item Type:	Article
Additional Information:	This is open access article
Subjects:	Infection and Immunity
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	22 Jan 2021 09:55
Last Modified:	29 Nov 2021 10:49
URI:	http://nccs.sciencecentral.in/id/eprint/878

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