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Structure of a major immunogenic site on foot-and-mouth disease virus
D Logan1, R Abu-Ghazaleh, W Blakemore
1Laboratory of Molecular Biophysics, University of Oxford, UK.
Abstract:
Attachment of foot-and-mouth disease virus (FMDV) to its cellular receptor involves a long and highly antigenic loop containing the conserved sequence, Arg-Gly-Asp, a motif known to be a recognition element in many integrin-dependent cell adhesion processes. In our original crystal structure of FMDV the Arg-Gly-Asp-containing loop ('the loop'), located between beta-strands G and H of capsid protein VP1, was disordered and hence essentially invisible. We previously surmised that its disorder is enhanced by a disulphide bond linking the base of the loop (Cys 134) to Cys 130 of VP2 (ref. 8). We report here the crystal structure of the virus in which this disulphide is reduced. Reduced virus retains infectivity and serological experiments suggest that some of the loop's internal structure is conserved. But here its structure has become sufficiently ordered to allow us to describe an unambiguous conformation, which we relate to some key biological properties of the virus.
Insights
Foot-and-mouth disease virus (FMDV) attachment relies on a flexible loop. Reducing a disulfide bond orders this loop, revealing its structure and aiding understanding of FMDV biological properties.
Area of Science:
- Virology
- Structural Biology
- Biochemistry
Background:
- Foot-and-mouth disease virus (FMDV) attachment to cellular receptors is mediated by a highly antigenic loop on capsid protein VP1.
- This loop contains the Arg-Gly-Asp motif, crucial for integrin-dependent cell adhesion.
- Previous FMDV crystal structures showed this loop as disordered, hindering detailed analysis.
Purpose of the Study:
- To determine the ordered structure of the Arg-Gly-Asp-containing loop in FMDV.
- To investigate the role of a specific disulfide bond in loop disorder.
- To correlate the loop's structure with FMDV's biological properties.
Main Methods:
- Crystallography to determine the structure of FMDV with a reduced disulfide bond.
- Serological experiments to assess the conservation of loop structure.
- Analysis of the ordered loop conformation.
Main Results:
- The crystal structure of FMDV with a reduced disulfide bond was determined.
- The reduction of the disulfide bond (linking Cys 134 of VP1 to Cys 130 of VP2) led to the ordering of the Arg-Gly-Asp loop.
- The ordered loop adopted an unambiguous conformation, and the reduced virus retained infectivity.
Conclusions:
- Disulfide bond reduction is key to resolving the FMDV Arg-Gly-Asp loop structure.
- The ordered loop structure provides insights into FMDV-receptor interactions and biological functions.
- Understanding this loop's conformation is vital for FMDV research and control strategies.