Type IV pilus structure by cryo-electron microscopy and crystallography: implications for pilus assembly and
Lisa Craig1, Niels Volkmann, Andrew S Arvai
1Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
Molecular Cell
|September 5, 2006
Summary
Researchers revealed the detailed structure of Type IV pili (T4P) from Neisseria gonorrhoeae. This breakthrough clarifies how these bacterial filaments function and assemble, offering insights into pathogen virulence.
Area of Science:
- Microbiology
- Structural Biology
- Biophysics
Background:
- Type IV pili (T4P) are essential bacterial surface appendages involved in adhesion, motility, and DNA uptake.
- Neisseria gonorrhoeae T4P are critical virulence factors and targets for antibiotic resistance, but their detailed structure remains unknown.
- Understanding T4P structure is key to developing new therapeutic strategies against bacterial infections.
Purpose of the Study:
- To determine the high-resolution structure of native Neisseria gonorrhoeae Type IV pili.
- To elucidate the molecular mechanisms underlying T4P assembly, disassembly, and multifunctionality.
- To provide structural insights into T4P-mediated bacterial pathogenesis.
Main Methods:
- Cryo-electron microscopy (cryo-EM) was used to obtain a 12.5 Å resolution reconstruction of native GC-T4P.
- A 2.3 Å resolution crystal structure of the full-length pilin subunit was determined.
- Quantitative fitting of the pilin structure into the cryo-EM map enabled detailed structural analysis.
Main Results:
- The study reveals a core structure of spiraling three-helix bundles forming the T4P filament.
- Globular pilin heads are anchored by these bundles, providing strength and flexibility.
- Hypervariable loops and posttranslational modifications create a corrugated pilus surface, shielding conserved functional residues.
Conclusions:
- The determined structure clarifies the multifunctionality and dynamic assembly-disassembly of T4P.
- The findings suggest conserved assembly mechanisms across T4P, archaeal flagella, and type II secretion system filaments.
- This structural understanding aids in targeting T4P for novel antimicrobial strategies.
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