2i9l
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Medical countermeasures to prevent or treat smallpox are needed due to the | + | Medical countermeasures to prevent or treat smallpox are needed due to the potential use of poxviruses as biological weapons. Safety concerns with the currently available smallpox vaccine indicate a need for research on alternative poxvirus vaccine strategies. Molecular vaccines involving the use of proteins and/or genes and recombinant antibodies are among the strategies under current investigation. The poxvirus L1 protein, encoded by the L1R open reading frame, is the target of neutralizing antibodies and has been successfully used as a component of both protein subunit and DNA vaccines. L1-specific monoclonal antibodies (e.g., mouse monoclonal antibody mAb-7D11, mAb-10F5) with potent neutralizing activity bind L1 in a conformation-specific manner. This suggests that proper folding of the L1 protein used in molecular vaccines will affect the production of neutralizing antibodies and protection. Here, we co-crystallized the Fab fragment of mAb-7D11 with the L1 protein. The crystal structure of the complex between Fab-7D11 and L1 reveals the basis for the conformation-specific binding as recognition of a discontinuous epitope containing two loops that are held together by a disulfide bond. The structure of this important conformational epitope of L1 will contribute to the development of molecular poxvirus vaccines and also provides a novel target for anti-poxvirus drugs. In addition, the sequence and structure of Fab-7D11 will contribute to the development of L1-targeted immunotherapeutics. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | Structural basis for the binding of the neutralizing antibody, 7D11, to the poxvirus L1 protein., Su HP, Golden JW, Gittis AG, Hooper JW, Garboczi DN, Virology. 2007 | + | Structural basis for the binding of the neutralizing antibody, 7D11, to the poxvirus L1 protein., Su HP, Golden JW, Gittis AG, Hooper JW, Garboczi DN, Virology. 2007 Nov 25;368(2):331-41. Epub 2007 Aug 3. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17688903 17688903] |
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Vaccinia virus]] | [[Category: Vaccinia virus]] | ||
| - | [[Category: Garboczi, D | + | [[Category: Garboczi, D N.]] |
| - | [[Category: Gittis, A | + | [[Category: Gittis, A G.]] |
| - | [[Category: Golden, J | + | [[Category: Golden, J W.]] |
| - | [[Category: Hooper, J | + | [[Category: Hooper, J W.]] |
[[Category: Moss, B.]] | [[Category: Moss, B.]] | ||
| - | [[Category: Su, H | + | [[Category: Su, H P.]] |
[[Category: GOL]] | [[Category: GOL]] | ||
[[Category: antibody complex]] | [[Category: antibody complex]] | ||
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[[Category: poxvirus]] | [[Category: poxvirus]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:50:25 2008'' |
Revision as of 15:50, 21 February 2008
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Structure of Fab 7D11 from a neutralizing antibody against the poxvirus L1 protein
Overview
Medical countermeasures to prevent or treat smallpox are needed due to the potential use of poxviruses as biological weapons. Safety concerns with the currently available smallpox vaccine indicate a need for research on alternative poxvirus vaccine strategies. Molecular vaccines involving the use of proteins and/or genes and recombinant antibodies are among the strategies under current investigation. The poxvirus L1 protein, encoded by the L1R open reading frame, is the target of neutralizing antibodies and has been successfully used as a component of both protein subunit and DNA vaccines. L1-specific monoclonal antibodies (e.g., mouse monoclonal antibody mAb-7D11, mAb-10F5) with potent neutralizing activity bind L1 in a conformation-specific manner. This suggests that proper folding of the L1 protein used in molecular vaccines will affect the production of neutralizing antibodies and protection. Here, we co-crystallized the Fab fragment of mAb-7D11 with the L1 protein. The crystal structure of the complex between Fab-7D11 and L1 reveals the basis for the conformation-specific binding as recognition of a discontinuous epitope containing two loops that are held together by a disulfide bond. The structure of this important conformational epitope of L1 will contribute to the development of molecular poxvirus vaccines and also provides a novel target for anti-poxvirus drugs. In addition, the sequence and structure of Fab-7D11 will contribute to the development of L1-targeted immunotherapeutics.
About this Structure
2I9L is a Single protein structure of sequence from Mus musculus and Vaccinia virus with as ligand. Full crystallographic information is available from OCA.
Reference
Structural basis for the binding of the neutralizing antibody, 7D11, to the poxvirus L1 protein., Su HP, Golden JW, Gittis AG, Hooper JW, Garboczi DN, Virology. 2007 Nov 25;368(2):331-41. Epub 2007 Aug 3. PMID:17688903
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