2PY0

Crystal structure of Cs1 pilin chimera

Summary for 2PY0

• Entry DOI: 10.2210/pdb2py0/pdb
• Related: 1DZO 1QVE
• Descriptor: Fimbrial protein, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID (3 entities in total)
• Functional Keywords: type iv pilus, consensus sequence, pseudomonas aeruginosa, monomeric pilin, cell adhesion
• Biological source: Pseudomonas aeruginosa
• Cellular location: Fimbrium: P02973
• Total number of polymer chains: 1
• Total formula weight: 12531.14

Authors

Kao, D.J.,Churchill, M.E.,Hodges, R.S. (deposition date: 2007-05-14, release date: 2007-11-06, Last modification date: 2024-11-13)

Primary citation

Kao, D.J.,Churchill, M.E.,Irvin, R.T.,Hodges, R.S.
Animal Protection and Structural Studies of a Consensus Sequence Vaccine Targeting the Receptor Binding Domain of the Type IV Pilus of Pseudomonas aeruginosa.
J.Mol.Biol., 374:426-442, 2007

PubMed Abstract: 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.

PubMed: 17936788
DOI: 10.1016/j.jmb.2007.09.032

Experimental method

X-RAY DIFFRACTION (1.35 Å)