Chaperone-assisted assembly and molecular architecture of adhesive pili.
The assembly of bacterial pili as exemplified here by P and type 1 pili of E. coli is a complex process involving specific molecular interactions between structural and chaperone proteins. The assembly process occurs postsecretionally, i.e. after the subunits are translocated across the cytoplasmic membrane. In a single cell, hundreds of thousands of interactive subunits are typically surface localized and assembled into pili. Periplasmic chaperones are generally required to bind to the interactive subunits and partition them into assembly-competent complexes. The binding of the chaperone to the subunits apparently protects the interactive surfaces and prevents them from aggregating at the wrong time and place within the cell. Pili are most likely assembled into linear polymers that package into right-handed helices after their translocation through specific outer-membrane channels. Each pilus filament is a quaternary assembly of the structural subunit and several minor subunits including the adhesin moiety. Although the assembly and organization of P and type 1 pili are very similar, there are some notable differences. For example, the P pilus adhesin is located exclusively at the tips of the pilus filament and forms part of a morphologically distinct structure. In contrast, the adhesion moiety of type 1 pili is inserted into the pilus filament at intervals, but only the adhesin molecule exposed at the pilus tip is functional. The variability in isoreceptor recognition amongst P pili has been solely ascribed to structural differences in the respective adhesin molecules, whereas in type 1 pili, variability in binding specificity has been attributed to the pilus filament that influences the conformation of the adhesin moiety. Less is known about the structure or assembly of type 4 pili, which are a unique class of pili expressed by several different species of gram-negative bacteria. The phase variation of the pilC assembly gene in N. gonorrheae to the off state results in the accumulation of unassembled subunits toxic to the cells. This process exerts a strong selection pressure on the cells that triggers alterations in the pilin structural gene. Thus, antigenic variation of pili in this organism may be regulated at the level of assembly. Finally, the concept of periplasmic chaperones in postsecretional assembly is most likely a general phenomenon in the biology of gram-negative bacteria. The investigations of pilus assembly will continue to provide insight into the details of how macromolecular assembly reactions are coordinated in the bacterial cell and how the regulation of assembly genes can profoundly affect biological processes.
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110.
S J
SJ
Hultgren
S
S
Normark
S N
SN
Abraham
D018830:Adhesins, Escherichia coli; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D018833:Chaperonins; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure*; D010861:Fimbriae, Bacterial / Q000502:physiology* / Q000648:ultrastructure; D005810:Multigene Family; D009344:Neisseria gonorrhoeae / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure; D011506:Proteins / Q000502:physiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure; D014734:Vibrio cholerae / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure
D018830:Adhesins, Escherichia coli; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D011506:Proteins; D018833:Chaperonins