Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation

被引：45

作者：

Allen, Joel D. ^{[1
]}

Chawla, Himanshi ^{[1
]}

Samsudin, Firdaus ^{[2
]}

Zuzic, Lorena ^{[2
,19
]}

Shivgan, Aishwary Tukaram ^{[2
,18
]}

Watanabe, Yasunori ^{[1
]}

He, Wan-Ting ^{[3
,4
,5
]}

Callaghan, Sean ^{[3
,4
,5
]}

Song, Ge ^{[3
,4
,5
]}

Yong, Peter ^{[3
,4
,5
]}

Brouwer, Philip J. M. ^{[6
]}

Song, Yutong ^{[7
,8
]}

Cai, Yongfei ^{[9
]}

Duyvesteyn, Helen M. E. ^{[11
]}

Malinauskas, Tomas ^{[11
]}

Kint, Joeri ^{[12
]}

Pino, Paco ^{[12
]}

Wurm, Maria J. ^{[12
]}

Frank, Martin ^{[13
]}

Chen, Bing ^{[9
,10
]}

Stuart, David, I ^{[11
,14
]}

Sanders, Rogier W. ^{[6
,15
]}

Andrabi, Raiees ^{[3
,4
,5
]}

Burton, Dennis R. ^{[3
,4
,5
,16
,17
]}

Li, Sai ^{[7
,8
]}

Bond, Peter J. ^{[2
,18
]}

Crispin, Max ^{[1
]}

机构：

[1] Univ Southampton, Sch Biol Sci, Southampton SO17 1BJ, Hants, England

[2] ASTAR, Bioinformat Inst, Singapore 138671, Singapore

[3] Scripps Res Inst, Dept Immunol & Microbiol, La Jolla, CA 92037 USA

[4] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA

[5] Scripps Res Inst, Consortium HIV AIDS Vaccine Dev CHAVD, La Jolla, CA 92037 USA

[6] Univ Amsterdam, Amsterdam Infect & Immun Inst, Dept Med Microbiol, Amsterdam UMC, Amsterdam, Netherlands

[7] Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Sch Life Sci, Beijing 100084, Peoples R China

[8] Beijing Adv Innovat Ctr Struct Biol & Frontier Re, Beijing 100084, Peoples R China

[9] Boston Childrens Hosp, Div Mol Med, Boston, MA 02115 USA

[10] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA

[11] Univ Oxford, Wellcome Ctr Human Genet, Div Struct Biol, Oxford OX3 7BN, England

[12] ExcellGene SA, CH-1870 Monthey, Switzerland

[13] Biognos AB, S-41705 Gothenburg, Sweden

[14] Diamond Light Source Ltd, Harwell Sci & Innovat Campus, Didcot OX11 0DE, Oxon, England

[15] Cornell Univ, Dept Microbiol & Immunol, Weill Med Coll, New York, NY USA

[16] MIT, Ragon Inst, Massachusetts Gen Hosp, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[17] Harvard Univ, Cambridge, MA 02139 USA

[18] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore

[19] Univ Manchester, Fac Sci & Engn, Manchester Inst Biotechnol, Dept Chem, Manchester, Lancs, England

来源：

BIOCHEMISTRY | 2021年 / 60卷 / 27期

基金：

美国国家卫生研究院; 英国医学研究理事会; 英国惠康基金;

关键词：

HIV-1; CELL; DYNAMICS; GLYCOPROTEIN; RECOGNITION; LIPIDS;

D O I：

10.1021/acs.biochem.1c00279

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity. The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation. Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells. We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure. Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans. These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.

引用

页码：2153 / 2169

页数：17

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