Insights from NMR Spectroscopy into the Conformational Properties of Man-9 and Its Recognition by Two HIV Binding Proteins

Overview

Journal Chembiochem

Specialty Biochemistry

Date 2017 Feb 7

PMID 28166380

Citations 12

Authors

Syed Shahzad-Ul-Hussan

Mallika Sastry

Thomas Lemmin

Cinque Soto

Sandra Loesgen

Danielle A Scott

Jack R Davison

Katheryn Lohith

Robert OConnor

Peter D Kwong

Carole A Bewley

Affiliations

Soon will be listed here.

Abstract

Man GlcNAc (Man-9) present at the surface of HIV makes up the binding sites of several HIV-neutralizing agents and the mammalian lectin DC-SIGN, which is involved in cellular immunity and trans-infections. We describe the conformational properties of Man-9 in its free state and when bound by the HIV entry-inhibitor protein microvirin (MVN), and define the minimum epitopes of both MVN and DC-SIGN by using NMR spectroscopy. To facilitate the implementation of 3D C-edited spectra to deconvolute spectral overlap and to determine the solution structure of Man-9, we developed a robust expression system for the production of C, N-labeled glycans in mammalian cells. The studies reveal that Man-9 interacts with HIV-binding proteins through distinct epitopes and adopts diverse conformations in the bound state. In combination with molecular dynamics simulations we observed receptor-bound conformations to be sampled by Man-9 in the free state, thus suggesting a conformational selection mechanism for diverse recognition.

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References

Snyder G, Colonna M, Sun P . The structure of DC-SIGNR with a portion of its repeat domain lends insights to modeling of the receptor tetramer. J Mol Biol. 2005; 347(5):979-89. PMC: 7094344. DOI: 10.1016/j.jmb.2005.01.063. View

. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Symbols for specifying the conformation of polysaccharide chains. Recommendations 1981. Eur J Biochem. 1983; 131(1):5-7. DOI: 10.1111/j.1432-1033.1983.tb07224.x. View

Angulo J, Rademacher C, Biet T, Benie A, Blume A, Peters H . NMR analysis of carbohydrate-protein interactions. Methods Enzymol. 2006; 416:12-30. DOI: 10.1016/S0076-6879(06)16002-4. View

Woods R . Three-dimensional structures of oligosaccharides. Curr Opin Struct Biol. 1995; 5(5):591-8. DOI: 10.1016/0959-440x(95)80049-2. View

Shahzad-Ul-Hussan S, Gustchina E, Ghirlando R, Clore G, Bewley C . Solution structure of the monovalent lectin microvirin in complex with Man(alpha)(1-2)Man provides a basis for anti-HIV activity with low toxicity. J Biol Chem. 2011; 286(23):20788-96. PMC: 3121468. DOI: 10.1074/jbc.M111.232678. View

Doores K . The HIV glycan shield as a target for broadly neutralizing antibodies. FEBS J. 2015; 282(24):4679-91. PMC: 4950053. DOI: 10.1111/febs.13530. View

Kamiya Y, Yamamoto S, Chiba Y, Jigami Y, Kato K . Overexpression of a homogeneous oligosaccharide with 13C labeling by genetically engineered yeast strain. J Biomol NMR. 2011; 50(4):397-401. DOI: 10.1007/s10858-011-9525-1. View

Schwieters C, Kuszewski J, Tjandra N, Clore G . The Xplor-NIH NMR molecular structure determination package. J Magn Reson. 2003; 160(1):65-73. DOI: 10.1016/s1090-7807(02)00014-9. View

Yang F, Bewley C, Louis J, Gustafson K, Boyd M, Gronenborn A . Crystal structure of cyanovirin-N, a potent HIV-inactivating protein, shows unexpected domain swapping. J Mol Biol. 1999; 288(3):403-12. DOI: 10.1006/jmbi.1999.2693. View

10.

Wu L, Yang Z, Xu L, Welcher B, Winfrey S, Shao Y . Cross-clade recognition and neutralization by the V3 region from clade C human immunodeficiency virus-1 envelope. Vaccine. 2006; 24(23):4995-5002. DOI: 10.1016/j.vaccine.2006.03.083. View

11.

Kato K, Yamaguchi Y, Arata Y . Stable-isotope-assisted NMR approaches to glycoproteins using immunoglobulin G as a model system. Prog Nucl Magn Reson Spectrosc. 2010; 56(4):346-59. DOI: 10.1016/j.pnmrs.2010.03.001. View

12.

Yamaguchi T, Sakae Y, Zhang Y, Yamamoto S, Okamoto Y, Kato K . Exploration of conformational spaces of high-mannose-type oligosaccharides by an NMR-validated simulation. Angew Chem Int Ed Engl. 2014; 53(41):10941-4. DOI: 10.1002/anie.201406145. View

13.

OKeefe B, Vojdani F, Buffa V, Shattock R, Montefiori D, Bakke J . Scaleable manufacture of HIV-1 entry inhibitor griffithsin and validation of its safety and efficacy as a topical microbicide component. Proc Natl Acad Sci U S A. 2009; 106(15):6099-104. PMC: 2662964. DOI: 10.1073/pnas.0901506106. View

14.

Feinberg H, Castelli R, Drickamer K, Seeberger P, Weis W . Multiple modes of binding enhance the affinity of DC-SIGN for high mannose N-linked glycans found on viral glycoproteins. J Biol Chem. 2006; 282(6):4202-9. PMC: 2277367. DOI: 10.1074/jbc.M609689200. View

15.

Sastry M, Bewley C, Kwong P . Effective isotope labeling of proteins in a mammalian expression system. Methods Enzymol. 2015; 565:289-307. PMC: 6260808. DOI: 10.1016/bs.mie.2015.09.021. View

16.

Joyce M, Kanekiyo M, Xu L, Biertumpfel C, Boyington J, Moquin S . Outer domain of HIV-1 gp120: antigenic optimization, structural malleability, and crystal structure with antibody VRC-PG04. J Virol. 2012; 87(4):2294-306. PMC: 3571475. DOI: 10.1128/JVI.02717-12. View

17.

Mari S, Sanchez-Medina I, Mereghetti P, Belvisi L, Jimenez-Barbero J, Bernardi A . Synthesis and conformational analysis of an alpha-D-mannopyranosyl-(1-->2)-alpha-D-mannopyranosyl-(1-->6)-alpha-D-mannopyranose mimic. Carbohydr Res. 2007; 342(12-13):1859-68. DOI: 10.1016/j.carres.2007.03.019. View

18.

Pejchal R, Doores K, Walker L, Khayat R, Huang P, Wang S . A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science. 2011; 334(6059):1097-103. PMC: 3280215. DOI: 10.1126/science.1213256. View

19.

Wormald M, Petrescu A, Glithero A, Elliott T, Dwek R . Conformational studies of oligosaccharides and glycopeptides: complementarity of NMR, X-ray crystallography, and molecular modelling. Chem Rev. 2002; 102(2):371-86. DOI: 10.1021/cr990368i. View

20.

Garces F, Sok D, Kong L, McBride R, Kim H, Saye-Francisco K . Structural evolution of glycan recognition by a family of potent HIV antibodies. Cell. 2014; 159(1):69-79. PMC: 4278586. DOI: 10.1016/j.cell.2014.09.009. View