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Structure and Carbohydrate Recognition by the Nonmitogenic Lectin Horcolin

Narayanan, V and Bobbili, KB and Sivaji, N and Jayaprakash, NG and Suguna, K and Surolia, A and Sekhar, A (2022) Structure and Carbohydrate Recognition by the Nonmitogenic Lectin Horcolin. In: Biochemistry, 61 (6). pp. 464-478.

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Official URL: https://doi.org/10.1021/acs.biochem.1c00778


Lectins are sugar-binding proteins that have shown considerable promise as antiviral agents because of their ability to interact with envelope glycoproteins present on the surface of viruses such as HIV-1. However, their therapeutic potential has been compromised by their mitogenicity that stimulates uncontrolled division of T-lymphocytes. Horcolin, a member of the jacalin family of lectins, tightly binds the HIV-1 envelope glycoprotein gp120 and neutralizes HIV-1 particles but is nonmitogenic. In this report, we combine X-ray crystallography and NMR spectroscopy to obtain atomic-resolution insights into the structure of horcolin and the molecular basis for its carbohydrate recognition. Each protomer of the horcolin dimer adopts a canonical β-prism I fold with three Greek key motifs and carries two carbohydrate-binding sites. The carbohydrate molecule binds in a negatively charged pocket and is stabilized by backbone and side chain hydrogen bonds to conserved residues in the ligand-binding loop. NMR titrations reveal a two-site binding mode and equilibrium dissociation constants for the two binding sites determined from two-dimensional (2D) lineshape modeling are 4-fold different. Single-binding-site variants of horcolin confirm the dichotomy in binding sites and suggest that there is allosteric communication between the two sites. An analysis of the horcolin structure shows a network of hydrogen bonds linking the two carbohydrate-binding sites directly and through a secondary binding site, and this coupling between the two sites is expected to assume importance in the interaction of horcolin with high-mannose glycans found on viral envelope glycoproteins.

Item Type: Journal Article
Publication: Biochemistry
Publisher: American Chemical Society
Additional Information: The copyright for this article belongs to the Authors.
Keywords: Binding energy; Carbohydrates; Dimers; Dissociation; Equilibrium constants; Glycoproteins; Hydrogen bonds; Nuclear magnetic resonance spectroscopy; Proteins; Viruses; X ray crystallography, Binding-sites; Carbohydrate binding; Carbohydrate recognition; Envelope glycoproteins; Jacalin; Structure recognition; Sugar-binding protein; T lymphocytes; Therapeutic potentials; Uncontrolled division, Binding sites
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 12 May 2022 11:29
Last Modified: 16 Jun 2022 07:16
URI: https://eprints.iisc.ac.in/id/eprint/71661

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