Structure of the complex of an Fab fragment of a neutralizing antibody with foot-and-mouth disease virus: Positioning of a highly mobile antigenic loop

被引:82
作者
Hewat, EA
Verdaguer, N
Fita, I
Blakemore, W
Brookes, S
King, A
Newman, J
Domingo, E
Mateu, MG
Stuart, DI
机构
[1] CSIC,CID,DEPT BIOL MOL & CELULAR,ES-08034 BARCELONA,SPAIN
[2] AFRC,INST ANIM HLTH,PIRBRIGHT LAB,PIRBRIGHT GU24 0NF,SURREY,ENGLAND
[3] UNIV AUTONOMA MADRID,CSIC,CTR BIOL MOL SEVERO OCHOA,E-28049 MADRID,SPAIN
[4] UNIV OXFORD,MOL BIOPHYS LAB,OXFORD OX1 3QU,ENGLAND
[5] UNIV OXFORD,OXFORD CTR MOL SCI,OXFORD OX1 3QT,ENGLAND
关键词
antigenicity; cryo-electron microscopy; crystallography; foot-and-mouth disease virus; virus-Fab structures;
D O I
10.1093/emboj/16.7.1492
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
Data from cryo-electron microscopy and X-ray crystallography have been combined to study the interactions of foot-and-mouth disease virus serotype C (FMDV-C) with a strongly neutralizing monoclonal antibody (mAb) SD6. The mAb SDG binds to the long flexible GH-loop of viral protein 1 (VP1) which also binds to an integrin receptor. The structure of the virus-Fab complex was determined to 30 Angstrom resolution using cryo-electron microscopy and image analysis. The known structure Of FMDV-C, and of the SD6 Fab co-crystallized with a synthetic peptide corresponding to the GH-loop of VP1, were fitted to the cryo-electron microscope density map. The SD6 Fab is seen to project almost radially from the viral surface in an orientation which is only compatible with monovalent binding of the mAb. Even taking into account the mAb hinge and elbow flexibility, it is not possible to model bivalent binding without severely distorting the Fabs. The bound GN-loop is essentially in what has previously been termed the 'up' position in the best fit Fab orientation. The SD6 Fab interacts almost exclusively with the GN-loop of VP1, making very few other contacts with the viral capsid. The position and orientation of the SD6 Fab bound to FMDV-C is in accord with previous immunogenic data.
引用
收藏
页码:1492 / 1500
页数:9
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