Distinct dissociation rates of murine and human norovirus P-domain dimers suggest a role of dimer stability in virus-host interactions

被引：6

作者：

Creutznacher, Robert ^{[1
,8
]}

Maass, Thorben ^{[1
]}

Dulfer, Jasmin ^{[2
]}

Feldmann, Clara ^{[1
]}

Hartmann, Veronika ^{[3
]}

Lane, Miranda Sophie ^{[3
]}

Knickmann, Jan ^{[3
]}

Westermann, Leon Torben ^{[1
]}

Thiede, Lars ^{[2
,4
]}

Smith, Thomas J. ^{[5
]}

Uetrecht, Charlotte ^{[2
,4
,6
]}

Mallagaray, Alvaro ^{[1
]}

Waudby, Christopher A. ^{[7
]}

Taube, Stefan ^{[3
]}

Peters, Thomas ^{[1
]}

机构：

[1] Univ Lubeck, Ctr Struct & Cell Biol Med CSCM, Inst Chem & Metabol, Ratzeburger Allee 160, D-23562 Lubeck, Germany

[2] Leibniz Inst Virol LIV, Martinistr 52, D-20251 Hamburg, Germany

[3] Univ Lubeck, Inst Virol & Cell Biol, Ctr Struct & Cell Biol Med CSCM, Ratzeburger Allee 160, D-23562 Lubeck, Germany

[4] Deutsch Elektronen Synchrotron DESY, CSSB Ctr Struct Syst Biol, Notkestr 85, D-22607 Hamburg, Germany

[5] Univ Texas Med Branch, Dept Biochem & Mol Biol, 301 Univ Blvd,Route 0645, Galveston, TX 77555 USA

[6] Univ Siegen, Sch Life Sci, D-57076 Siegen, Germany

[7] UCL, Inst Struct & Mol Biol, Gower St, London WC1E 6BT, England

[8] Univ Utrecht, Fac Vet Med, Dept Infect Dis & Immunol, Virol Div, Yalelaan 1, NL-3584 CL Utrecht, Netherlands

来源：

COMMUNICATIONS BIOLOGY | 2022年 / 5卷 / 01期

关键词：

MOLECULAR-WEIGHT PROTEINS; NMR-SPECTROSCOPY; METHYL-GROUPS; TROSY; RECEPTOR; DIMERIZATION; REPLICATION; MULTIPLE; DYNAMICS; SINGLE;

D O I：

10.1038/s42003-022-03497-4

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Norovirus capsids are icosahedral particles composed of 90 dimers of the major capsid protein VP1. The C-terminus of the VP1 proteins forms a protruding (P)-domain, mediating receptor attachment, and providing a target for neutralizing antibodies. NMR and native mass spectrometry directly detect P-domain monomers in solution for murine (MNV) but not for human norovirus (HuNoV). We report that the binding of glycochenodeoxycholic acid (GCDCA) stabilizes MNV-1 P-domain dimers (P-dimers) and induces long-range NMR chemical shift perturbations (CSPs) within loops involved in antibody and receptor binding, likely reflecting corresponding conformational changes. Global line shape analysis of monomer and dimer cross-peaks in concentration-dependent methyl TROSY NMR spectra yields a dissociation rate constant k(off) of about 1 s(-1) for MNV-1 P-dimers. For structurally closely related HuNoV GII.4 Saga P-dimers a value of about 10(-6 )s(-1) is obtained from ion-exchange chromatography, suggesting essential differences in the role of GCDCA as a cofactor for MNV and HuNoV infection. NMR and native mass spectrometry reveal that the major capsid VP1 protein from murine and human norovirus exhibit distinct behaviors and are differentially regulated by the binding of glycochenodeoxycholic acid.

引用

页数：13