The Tetrameric Plant Lectin BanLec Neutralizes HIV through Bidentate Binding to Specific Viral Glycans

Jonathan T.S. Hopper; Stephen Ambrose; Oliver C. Grant; Stefanie A. Krumm; Timothy M. Allison; Matteo T. Degiacomi; Mark D. Tully; Laura K. Pritchard; Gabriel Ozorowski; Andrew B. Ward; Max Crispin; Katie J. Doores; Robert J. Woods; Justin L.P. Benesch; Carol V. Robinson; Weston B. Struwe

doi:10.1016/j.str.2017.03.015

The Tetrameric Plant Lectin BanLec Neutralizes HIV through Bidentate Binding to Specific Viral Glycans

Jonathan T.S. Hopper, Stephen Ambrose, Oliver C. Grant, Stefanie A. Krumm, Timothy M. Allison, Matteo T. Degiacomi, Mark D. Tully, Laura K. Pritchard, Gabriel Ozorowski, Andrew B. Ward, Max Crispin, Katie J. Doores, Robert J. Woods, Justin L.P. Benesch, Carol V. Robinson, Weston B. Struwe

Infectious Diseases

Research output: Contribution to journal › Article › peer-review

38 Citations (Scopus)

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Abstract

Summary Select lectins have powerful anti-viral properties that effectively neutralize HIV-1 by targeting the dense glycan shield on the virus. Here, we reveal the mechanism by which one of the most potent lectins, BanLec, achieves its inhibition. We identify that BanLec recognizes a subset of high-mannose glycans via bidentate interactions spanning the two binding sites present on each BanLec monomer that were previously considered separate carbohydrate recognition domains. We show that both sites are required for high-affinity glycan binding and virus neutralization. Unexpectedly we find that BanLec adopts a tetrameric stoichiometry in solution whereby the glycan-binding sites are positioned to optimally target glycosylated viral spikes. The tetrameric architecture, together with bidentate binding to individual glycans, leads to layers of multivalency that drive viral neutralization through enhanced avidity effects. These structural insights will prove useful in engineering successful lectin therapeutics targeting the dense glycan shield of HIV.

Original language	English
Pages (from-to)	773-782.e5
Journal	Structure
Volume	25
Issue number	5
Early online date	20 Apr 2017
DOIs	https://doi.org/10.1016/j.str.2017.03.015
Publication status	E-pub ahead of print - 20 Apr 2017

Keywords

HIV
BanLec
Env
lectin
glycosylation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.str.2017.03.015

The tetrameric plant lectin_HOPPER_Publishedonline20April2017_GREEN AAMAccepted author manuscript, 358 KB

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Hopper, J. T. S., Ambrose, S., Grant, O. C., Krumm, S. A., Allison, T. M., Degiacomi, M. T., Tully, M. D., Pritchard, L. K., Ozorowski, G., Ward, A. B., Crispin, M., Doores, K. J., Woods, R. J., Benesch, J. L. P., Robinson, C. V., & Struwe, W. B. (2017). The Tetrameric Plant Lectin BanLec Neutralizes HIV through Bidentate Binding to Specific Viral Glycans. Structure, 25(5), 773-782.e5. Advance online publication. https://doi.org/10.1016/j.str.2017.03.015

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abstract = "Summary Select lectins have powerful anti-viral properties that effectively neutralize HIV-1 by targeting the dense glycan shield on the virus. Here, we reveal the mechanism by which one of the most potent lectins, BanLec, achieves its inhibition. We identify that BanLec recognizes a subset of high-mannose glycans via bidentate interactions spanning the two binding sites present on each BanLec monomer that were previously considered separate carbohydrate recognition domains. We show that both sites are required for high-affinity glycan binding and virus neutralization. Unexpectedly we find that BanLec adopts a tetrameric stoichiometry in solution whereby the glycan-binding sites are positioned to optimally target glycosylated viral spikes. The tetrameric architecture, together with bidentate binding to individual glycans, leads to layers of multivalency that drive viral neutralization through enhanced avidity effects. These structural insights will prove useful in engineering successful lectin therapeutics targeting the dense glycan shield of HIV.",

keywords = "HIV, BanLec, Env, lectin, glycosylation",

author = "Hopper, {Jonathan T.S.} and Stephen Ambrose and Grant, {Oliver C.} and Krumm, {Stefanie A.} and Allison, {Timothy M.} and Degiacomi, {Matteo T.} and Tully, {Mark D.} and Pritchard, {Laura K.} and Gabriel Ozorowski and Ward, {Andrew B.} and Max Crispin and Doores, {Katie J.} and Woods, {Robert J.} and Benesch, {Justin L.P.} and Robinson, {Carol V.} and Struwe, {Weston B.}",

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Hopper, JTS, Ambrose, S, Grant, OC, Krumm, SA, Allison, TM, Degiacomi, MT, Tully, MD, Pritchard, LK, Ozorowski, G, Ward, AB, Crispin, M, Doores, KJ, Woods, RJ, Benesch, JLP, Robinson, CV & Struwe, WB 2017, 'The Tetrameric Plant Lectin BanLec Neutralizes HIV through Bidentate Binding to Specific Viral Glycans', Structure, vol. 25, no. 5, pp. 773-782.e5. https://doi.org/10.1016/j.str.2017.03.015

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T1 - The Tetrameric Plant Lectin BanLec Neutralizes HIV through Bidentate Binding to Specific Viral Glycans

AU - Hopper, Jonathan T.S.

AU - Ambrose, Stephen

AU - Grant, Oliver C.

AU - Krumm, Stefanie A.

AU - Allison, Timothy M.

AU - Degiacomi, Matteo T.

AU - Tully, Mark D.

AU - Pritchard, Laura K.

AU - Ozorowski, Gabriel

AU - Ward, Andrew B.

AU - Crispin, Max

AU - Doores, Katie J.

AU - Woods, Robert J.

AU - Benesch, Justin L.P.

AU - Robinson, Carol V.

AU - Struwe, Weston B.

PY - 2017/4/20

Y1 - 2017/4/20

N2 - Summary Select lectins have powerful anti-viral properties that effectively neutralize HIV-1 by targeting the dense glycan shield on the virus. Here, we reveal the mechanism by which one of the most potent lectins, BanLec, achieves its inhibition. We identify that BanLec recognizes a subset of high-mannose glycans via bidentate interactions spanning the two binding sites present on each BanLec monomer that were previously considered separate carbohydrate recognition domains. We show that both sites are required for high-affinity glycan binding and virus neutralization. Unexpectedly we find that BanLec adopts a tetrameric stoichiometry in solution whereby the glycan-binding sites are positioned to optimally target glycosylated viral spikes. The tetrameric architecture, together with bidentate binding to individual glycans, leads to layers of multivalency that drive viral neutralization through enhanced avidity effects. These structural insights will prove useful in engineering successful lectin therapeutics targeting the dense glycan shield of HIV.

AB - Summary Select lectins have powerful anti-viral properties that effectively neutralize HIV-1 by targeting the dense glycan shield on the virus. Here, we reveal the mechanism by which one of the most potent lectins, BanLec, achieves its inhibition. We identify that BanLec recognizes a subset of high-mannose glycans via bidentate interactions spanning the two binding sites present on each BanLec monomer that were previously considered separate carbohydrate recognition domains. We show that both sites are required for high-affinity glycan binding and virus neutralization. Unexpectedly we find that BanLec adopts a tetrameric stoichiometry in solution whereby the glycan-binding sites are positioned to optimally target glycosylated viral spikes. The tetrameric architecture, together with bidentate binding to individual glycans, leads to layers of multivalency that drive viral neutralization through enhanced avidity effects. These structural insights will prove useful in engineering successful lectin therapeutics targeting the dense glycan shield of HIV.

KW - HIV

KW - BanLec

KW - Env

KW - lectin

KW - glycosylation

U2 - 10.1016/j.str.2017.03.015

DO - 10.1016/j.str.2017.03.015

M3 - Article

SN - 0969-2126

VL - 25

SP - 773-782.e5

JO - Structure

JF - Structure

IS - 5

ER -

The Tetrameric Plant Lectin BanLec Neutralizes HIV through Bidentate Binding to Specific Viral Glycans

Abstract

Keywords

UN SDGs

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