2py0
From Proteopedia
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'''Crystal structure of Cs1 pilin chimera''' | '''Crystal structure of Cs1 pilin chimera''' | ||
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[[Category: Hodges, R S.]] | [[Category: Hodges, R S.]] | ||
[[Category: Kao, D J.]] | [[Category: Kao, D J.]] | ||
| - | [[Category: | + | [[Category: Cell adhesion]] |
| - | [[Category: | + | [[Category: Consensus sequence]] |
| - | [[Category: | + | [[Category: Monomeric pilin]] |
| - | [[Category: | + | [[Category: Pseudomonas aeruginosa]] |
| - | [[Category: | + | [[Category: Type iv pilus]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 13:59:55 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 10:59, 4 May 2008
Crystal structure of Cs1 pilin chimera
Overview
One of the main obstacles in the development of a vaccine against Pseudomonas aeruginosa is the requirement that it is protective against a wide range of virulent strains. We have developed a synthetic-peptide consensus-sequence vaccine (Cs1) that targets the host receptor-binding domain (RBD) of the type IV pilus of P. aeruginosa. Here, we show that this vaccine provides increased protection against challenge by the four piliated strains that we have examined (PAK, PAO, KB7 and P1) in the A.BY/SnJ mouse model of acute P. aeruginosa infection. To further characterize the consensus sequence, we engineered Cs1 into the PAK monomeric pilin protein and determined the crystal structure of the chimeric Cs1 pilin to 1.35 A resolution. The substitutions (T130K and E135P) used to create Cs1 do not disrupt the conserved backbone conformation of the pilin RBD. In fact, based on the Cs1 pilin structure, we hypothesize that the E135P substitution bolsters the conserved backbone conformation and may partially explain the immunological activity of Cs1. Structural analysis of Cs1, PAK and K122-4 pilins reveal substitutions of non-conserved residues in the RBD are compensated for by complementary changes in the rest of the pilin monomer. Thus, the interactions between the RBD and the rest of the pilin can either be mediated by polar interactions of a hydrogen bond network in some strains or by hydrophobic interactions in others. Both configurations maintain a conserved backbone conformation of the RBD. Thus, the backbone conformation is critical in our consensus-sequence vaccine design and that cross-reactivity of the antibody response may be modulated by the composition of exposed side-chains on the surface of the RBD. This structure will guide our future vaccine design by focusing our investigation on the four variable residue positions that are exposed on the RBD surface.
About this Structure
2PY0 is a Single protein structure of sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA.
Reference
Animal protection and structural studies of a consensus sequence vaccine targeting the receptor binding domain of the type IV pilus of Pseudomonas aeruginosa., Kao DJ, Churchill ME, Irvin RT, Hodges RS, J Mol Biol. 2007 Nov 23;374(2):426-42. Epub 2007 Sep 19. PMID:17936788 Page seeded by OCA on Sun May 4 13:59:55 2008
