Discrete conformations of epitope II on the hepatitis C virus E2 protein for antibody-mediated neutralization and nonneutralization

被引：37

作者：

Deng, Lu ^{[1
]}

Ma, Li ^{[1
]}

Virata-Theimer, Maria Luisa ^{[1
]}

Zhong, Lilin ^{[1
]}

Yan, Hailing ^{[1
]}

Zhao, Zhong ^{[1
]}

Struble, Evi ^{[1
]}

Feinstone, Stephen ^{[2
]}

Alter, Harvey ^{[3
]}

Zhang, Pei ^{[1
]}

机构：

[1] US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Hematol, Bethesda, MD 20892 USA

[2] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Med, Washington, DC 20037 USA

[3] Warren Grant Magnuson Clin Ctr, Dept Transfus Med, NIH, Bethesda, MD 20892 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2014年 / 111卷 / 29期

基金：

美国国家卫生研究院;

关键词：

immunoglobulins; prophylaxis; vaccine; GP120; V3; LOOP; ALTERNATIVE CONFORMATIONS; BETA-HAIRPINS; BINDING; COMPLEXES; REGIONS;

D O I：

10.1073/pnas.1411317111

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The X-ray crystal structure of epitope II on the E2 protein of hepatitis C virus, in complex with nonneutralizing antibody mAb#12, has been solved at 2.90-angstrom resolution. The spatial arrangement of the essential components of epitope II (ie, the C-terminal a-helix and the N-terminal loop) was found to deviate significantly from that observed in those corresponding complexes with neutralizing antibodies. The distinct conformations are mediated largely by the flexibility of a highly conserved glycine residue that connects these components. Thus, it is the particular tertiary structure of epitope II, which is presented in a spatial and temporal manner, that determines the specificity of antibody recognition and, consequently, the outcome of neutralization or nonneutralization.

引用

页码：10690 / 10695

页数：6

共 32 条

[1] Recovery, persistence, and sequelae in hepatitis C virus infection: A perspective on long-term outcome [J].

Alter, HJ ;

Seeff, LB .

SEMINARS IN LIVER DISEASE, 2000, 20 (01) :17-35

[2] THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY [J].

BAILEY, S .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 :760-763

[3] Nonneutralizing human antibody fragments against hepatitis C virus E2 glycoprotein modulate neutralization of binding activity of human recombinant Fabs [J].

Burioni, R ;

Bugli, F ;

Mancini, N ;

Rosa, D ;

Di Campli, C ;

Moroncini, G ;

Manzin, A ;

Abrignani, S ;

Varaldo, PE ;

Clementi, M ;

Fadda, G .

VIROLOGY, 2001, 288 (01) :29-35

[4]

Centers for Disease Control and Prevention, 2012, CDC HLTH INF INT TRA

[5]

Creighton T.E., 1994, Proteins. Structures and Molecular Properties, V2nd

[6] Structural evidence for a bifurcated mode of action in the antibody-mediated neutralization of hepatitis C virus [J].

Deng, Lu ;

Zhong, Lilin ;

Struble, Evi ;

Duan, Hongying ;

Ma, Li ;

Harman, Christine ;

Yan, Hailing ;

Virata-Theimer, Maria Luisa ;

Zhao, Zhong ;

Feinstone, Stephen ;

Alter, Harvey ;

Zhang, Pei .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (18) :7418-7422

[7] Completion of the entire hepatitis C virus life cycle in genetically humanized mice [J].

Dorner, Marcus ;

Horwitz, Joshua A. ;

Donovan, Bridget M. ;

Labitt, Rachael N. ;

Budell, William C. ;

Friling, Tamar ;

Vogt, Alexander ;

Catanese, Maria Teresa ;

Satoh, Takashi ;

Kawai, Taro ;

Akira, Shizuo ;

Law, Mansun ;

Rice, Charles M. ;

Ploss, Alexander .

NATURE, 2013, 501 (7466) :237-+

[8] A conserved Gly436-Trp-Leu-Ala-Gly-Leu-Phe-Tyr motif in hepatitis C virus glycoprotein E2 is a determinant of CD81 binding and viral entry [J].

Drummer, Heidi E. ;

Boo, Irene ;

Maerz, Anne L. ;

Poumbourios, Pantelis .

JOURNAL OF VIROLOGY, 2006, 80 (16) :7844-7853

[9] Amino Acid Residue-Specific Neutralization and Nonneutralization of Hepatitis C Virus by Monoclonal Antibodies to the E2 Protein [J].

Duan, Hongying ;

Kachko, Alla ;

Zhong, Lilin ;

Struble, Evi ;

Pandey, Shivani ;

Yan, Hailing ;

Harman, Christine ;

Virata-Theimer, Maria Luisa ;

Deng, Lu ;

Zhao, Zhong ;

Major, Marian ;

Feinstone, Stephen ;

Zhang, Pei .

JOURNAL OF VIROLOGY, 2012, 86 (23) :12686-12694

[10] Features and development of Coot [J].

Emsley, P. ;

Lohkamp, B. ;

Scott, W. G. ;

Cowtan, K. .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 2010, 66 :486-501

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