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  • Review Article
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Type IV pilus structure and bacterial pathogenicity

Nature Reviews Microbiology volume 2, pages 363–378 (2004)Cite this article

Key Points

  • Type IV pili are strong, flexible filaments with varied roles in bacterial pathogenicity. Pilin structures and models are integrated here in a comprehensive review of the molecular basis of the assembly and multi-functionality of these filaments.

  • Type IV pili are grouped together as a class on the basis of sequence similarity of their major subunit protein, pilin, which has an unusual N-methylated amino terminus, a conserved hydrophobic N-terminal 25 residues, and a carboxy-terminal disulphide bond and can be divided into two subclasses, type IVa and type IVb. Type IVa pili occur on a wide range of Gram-negative bacteria, but so far, type IVb are restricted to human enteric bacteria.

  • The authors succinctly draw together the challenges that structural studies of type IV pili have presented, then review these structures and highlight specific structural features that are related to the assembly and function of type IV pili.

  • The authors present structure-based models for the type IVb toxin-co-regulated pilus (TCP) from Vibrio cholerae and the type IVa PAK pilus from Pseudomonas aeruginosa. These assembly models are surprisingly similar despite substantial differences in protein sequence, size and structure between the pilin subunits, and lead to a generalized assembly model for type IV pili. The PAK pilus model is presented here for the first time.

  • There are striking similarities between type IV pilus, archaeal flagellar and the type II secretion systems of bacteria. Archaeal flagella are required for motility, and type II secretion systems encode the machinery to export enzymes and toxins. How type IV pilus biogenesis and structure could help to generate hypotheses about the function of the archaeal flagellum and type II secretion systems are discussed.

  • The authors elaborate on the multiple functions of the type IV pili, which include adhesion to surfaces, immune escape, surface motility, microcolony formation, transformation and phage transduction, signalling to eukaryotic cells, apoptosis and complement inhibition, and in each case describe how the knowledge of type IV pilus structure and assembly can help us to understand these processes.

Abstract

Type IV pili are remarkably strong, flexible filaments with varied roles in bacterial pathogenicity. All Gram-negative bacterial surfaces have type IV pili, which are polymeric assemblies of the protein pilin that evoke the host immune response and are potential drug and vaccine targets. Pilin structures that have been solved using X-ray crystallography and nuclear magnetic resonance, together with models for pilus architectures inferred from electron microscopy, fibre diffraction and computation, have established a molecular basis for assembly and multi-functionality, with implications for therapeutic interventions.

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Figure 1: Type IV pili on Neisseria gonorrhoeae and Vibrio cholerae cells visualized by electron microscopy.
Figure 2: Structural comparisons of the type IV pilins.
Figure 3: Superposition of PAK pilin, GC pilin and TcpA showing the conserved structural core and the variable αβ-loop and D-region.
Figure 4: Negatively stained electron micrographs of PAK pili and TCP and their corresponding diffraction data.
Figure 5: Assembly models for PAK pili, TCP and the archaeal flagella from Halobacterium salinarum.
Figure 6: Stereo-view of the receptor-binding site in the D-region of PAK pilin.
Figure 7: Model for parallel versus antiparallel TCP interactions.

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Acknowledgements

We thank K. Forest and M. Donnenberg for valuable discussions, A. Yamagata, D. Shin and J. Huffman for comments, and the National Institute of Allergy and Infectious Diseases and the Canadian Institutes of Health Research for funding our research on type IV pilus structure and assembly.

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Authors and Affiliations

  1. Department of Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, 92037, California, USA

    Lisa Craig, Michael E. Pique & John A. Tainer

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  1. Lisa Craig
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DATABASES

Entrez

Bdellovibrio bacteriovorus

Dichelobacter nodosus

P. aeruginosa

Salmonella enterica serovar Typhi

The Protein Data Bank

flagella

flagellin

GC

K122-4 pilin

molecular model for TCP

PAK

PAK pilin

PapK

TcpA

FURTHER INFORMATION

Molecular models

Pilus retraction and twitching movies

John A. Tainer's laboratory

Glossary

AMPHIPATHIC

Having both hydrophobic and hydrophilic regions.

SCAFFOLD

A supporting structure.

SYMMETRY OPERATORS

A set of operations or moves, such as translations and rotations, about a symmetry axis, which convert one object into another apparently identical object.

AXIAL TRANSLATION

Also known as rise, it is the axial distance between one subunit and the next in a given start.

AZIMUTHAL ROTATION

Also known as twist, it is a rotation about the helical axis from one subunit to the next in a given start.

EQUATORIAL

A horizontal line through the centre of the diffraction pattern. can be compared with the meridian, which is a vertical line through the centre of the diffraction pattern.

MERIDIONAL INTENSITY

An intensity or layer line that coincides with the meridian of a diffraction pattern.

PITCH

The axial distance for one helical turn.

LAYER LINE

A pair of lines, arranged symmetrically about the origin of a diffraction pattern or Fourier transform that correspond to a helical wave. Layer lines are perpendicular to the direction of the helical axis and are spaced axially at multiples of the reciprocal of the helical pitch.

ONE-START

A one-start helix, also known as the 'genetic' or 'primitive' helix, is the helical path that connects every subunit with the smallest axial rotation.

THREE-START

A three-start helix is a set of three identical helices, all having the same pitch and number of subunits per turn, which together connect all subunits in the filament.

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Craig, L., Pique, M. & Tainer, J. Type IV pilus structure and bacterial pathogenicity. Nat Rev Microbiol 2, 363–378 (2004). https://doi.org/10.1038/nrmicro885

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