丙型肝炎病毒包膜糖蛋白 E2 抗原位点 412 至 423 与抗体 AP33 复合物的结构。
Structure of hepatitis C virus envelope glycoprotein E2 antigenic site 412 to 423 in complex with antibody AP33.
机构信息
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
出版信息
J Virol. 2012 Dec;86(23):13085-8. doi: 10.1128/JVI.01939-12. Epub 2012 Sep 12.
Abstract
We have determined the crystal structure of the broadly neutralizing antibody (bnAb) AP33, bound to a peptide corresponding to hepatitis C virus (HCV) E2 envelope glycoprotein antigenic site 412 to 423. Comparison with bnAb HCV1 bound to the same epitope reveals a different angle of approach to the antigen by bnAb AP33 and slight variation in its β-hairpin conformation of the epitope. These structures establish two different modes of binding to E2 that antibodies adopt to neutralize diverse HCV.
摘要
我们已经确定了广谱中和抗体（bnAb）AP33 与对应丙型肝炎病毒（HCV）E2 包膜糖蛋白抗原表位 412 至 423 的肽段结合的晶体结构。与结合同一表位的 bnAb HCV1 进行比较，揭示了 bnAb AP33 接近抗原的不同角度，以及其表位β发夹构象的轻微变化。这些结构确定了抗体采用的两种不同的结合 E2 的方式，以中和不同的 HCV。
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本文引用的文献
1
Structural basis of hepatitis C virus neutralization by broadly neutralizing antibody HCV1.
Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9499-504. doi: 10.1073/pnas.1202924109. Epub 2012 May 23.
2
Mutations within a conserved region of the hepatitis C virus E2 glycoprotein that influence virus-receptor interactions and sensitivity to neutralizing antibodies.
J Virol. 2010 Jun;84(11):5494-507. doi: 10.1128/JVI.02153-09. Epub 2010 Mar 17.
3
Identification and characterization of broadly neutralizing human monoclonal antibodies directed against the E2 envelope glycoprotein of hepatitis C virus.
J Virol. 2009 Dec;83(23):12473-82. doi: 10.1128/JVI.01138-09. Epub 2009 Sep 16.
4
HIV-1 and influenza antibodies: seeing antigens in new ways.
Nat Immunol. 2009 Jun;10(6):573-8. doi: 10.1038/ni.1746.
5
In vitro selection of a neutralization-resistant hepatitis C virus escape mutant.
Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19450-5. doi: 10.1073/pnas.0809879105. Epub 2008 Dec 3.
6
Structure-based antigen design: a strategy for next generation vaccines.
Trends Biotechnol. 2008 Dec;26(12):659-67. doi: 10.1016/j.tibtech.2008.08.002. Epub 2008 Oct 30.
7
Characterization of the hepatitis C virus E2 epitope defined by the broadly neutralizing monoclonal antibody AP33.
Hepatology. 2006 Mar;43(3):592-601. doi: 10.1002/hep.21088.
8
Monoclonal antibody AP33 defines a broadly neutralizing epitope on the hepatitis C virus E2 envelope glycoprotein.
J Virol. 2005 Sep;79(17):11095-104. doi: 10.1128/JVI.79.17.11095-11104.2005.
9
Antibodies, viruses and vaccines.
Nat Rev Immunol. 2002 Sep;2(9):706-13. doi: 10.1038/nri891.
10
Functional analysis of hepatitis C virus E2 glycoproteins and virus-like particles reveals structural dissimilarities between different forms of E2.
J Gen Virol. 2001 Aug;82(Pt 8):1877-1883. doi: 10.1099/0022-1317-82-8-1877.
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