Ultrahigh Resolution and Full-length Pilin Structures with Insights for Filament Assembly, Pathogenic Functions, and Vaccine Potential
| Autor: | Lisa Craig, Sophia Hartung, Subramaniapillai Kolappan, David S. Shin, Timothy I. Wood, John A. Tainer, Andrew S. Arvai |
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| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular Pilus assembly Polymers Protein Conformation Molecular Sequence Data Virulence Crystallography X-Ray Biochemistry Pilus Fimbriae Proteins Protein structure Bacterial Proteins Amino Acid Sequence Molecular Biology Francisella tularensis Sequence Homology Amino Acid biology Cell Biology biochemical phenomena metabolism and nutrition biology.organism_classification Cell biology Bacterial vaccine Dichelobacter nodosus Fimbriae Bacterial Pilin Protein Structure and Folding Bacterial Vaccines biology.protein bacteria |
| Zdroj: | Journal of Biological Chemistry. 286:44254-44265 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m111.297242 |
| Popis: | Pilin proteins assemble into Type IV pili (T4P), surface-displayed bacterial filaments with virulence functions including motility, attachment, transformation, immune escape, and colony formation. However, challenges in crystallizing full-length fiber-forming and membrane protein pilins leave unanswered questions regarding pilin structures, assembly, functions, and vaccine potential. Here we report pilin structures of full-length DnFimA from the sheep pathogen Dichelobacter nodosus and FtPilE from the human pathogen Francisella tularensis at 2.3 and 1 Å resolution, respectively. The DnFimA structure reveals an extended kinked N-terminal α-helix, an unusual centrally located disulfide, conserved subdomains, and assembled epitopes informing serogroup vaccines. An interaction between the conserved Glu-5 carboxyl oxygen and the N-terminal amine of an adjacent subunit in the crystallographic dimer is consistent with the hypothesis of a salt bridge between these groups driving T4P assembly. The FtPilE structure identifies an authentic Type IV pilin and provides a framework for understanding the role of T4P in F. tularensis virulence. Combined results define a unified pilin architecture, specialized subdomain roles in pilus assembly and function, and potential therapeutic targets. |
| Databáze: | OpenAIRE |
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