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Review
. 2021 Jul 14;22(14):7521.
doi: 10.3390/ijms22147521.

Bacterial Flagellar Filament: A Supramolecular Multifunctional Nanostructure

Marko Nedeljković  1 , Diego Emiliano Sastre  1 , Eric John Sundberg  1
Affiliations
Review

Bacterial Flagellar Filament: A Supramolecular Multifunctional Nanostructure

Marko Nedeljković et al. Int J Mol Sci. .

Abstract

The bacterial flagellum is a complex and dynamic nanomachine that propels bacteria through liquids. It consists of a basal body, a hook, and a long filament. The flagellar filament is composed of thousands of copies of the protein flagellin (FliC) arranged helically and ending with a filament cap composed of an oligomer of the protein FliD. The overall structure of the filament core is preserved across bacterial species, while the outer domains exhibit high variability, and in some cases are even completely absent. Flagellar assembly is a complex and energetically costly process triggered by environmental stimuli and, accordingly, highly regulated on transcriptional, translational and post-translational levels. Apart from its role in locomotion, the filament is critically important in several other aspects of bacterial survival, reproduction and pathogenicity, such as adhesion to surfaces, secretion of virulence factors and formation of biofilms. Additionally, due to its ability to provoke potent immune responses, flagellins have a role as adjuvants in vaccine development. In this review, we summarize the latest knowledge on the structure of flagellins, capping proteins and filaments, as well as their regulation and role during the colonization and infection of the host.

Keywords: FliD; bacterial flagella; filament; flagellin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structural characteristics of flagellins. (a) FliC monomer from S. Typhimurium with four distinct domain (PDB: 3A5X). Domains D0, D1 and D2 have N- and C-teminal moities, while D3 is formed by a continuous polypeptide sequence in the middle; (b) Structural alignment of D0 and D1 domains from various species showing high structural homology among them; (c) Outer domains of the C. jejuni flagellin FlaA and P. aeruginosa PAK type a FliC.
Figure 2
Figure 2
Cryo-EM structure of the flagellar filament from P. aeruginosa PAO1. (a) Cross-section of the left-handed filament consisting of 11 protofilaments. The inner tube (red) made of D0 domains and outer tube (cyan) together form the densely packed inner core of the filament. Outer domains are shown in green; (b) Left- and righ-handed filaments with all protofilaments tilted to the left and right from the central axis; (c) Helical symmetry lines in the filament. EMD: 8855, 8856.
Figure 3
Figure 3
FliD and the filament cap. (a) Structure of FliD from E. coli shows three domains (D1–D3) (PDB: 5H5V). The N- and C-termini are highly flexible and could not be resolved. (b) Structural alignment of FliD molecules from different species show high structural homology of D2 and D3 domains. FliD from H. pylori has two additional domains, D4 and D5. (c) Crystal structure of the filament cap from E. coli showing a hexameric structure. Domains D2 and D3 form the head region, while D1 (incomplete) forms the flexible leg region; (d) Oligomeric states of the crystallized FliD caps differ across species.
Figure 4
Figure 4
Genetic organization of main flagellar proteins involved in filament formation. The transcription of flagellar genes is hierarchical and controlled by different promoter classes that are temporally regulated. In peritrichous bacteria, flagellar genes are organized into three classes (I–III) and in monotrichous/polar bacteria the flagellar genes are organized into four classes, both starting with the transcription of the class I master regulator (MR*). Red arrows indicate the proteins and/or transcription factors responsible for the transcription activation of each corresponding class of flagellar genes. Black narrow arrows indicate positive activation/induction and black arrows with a vertical line tip (|) indicate inhibition. Genes involved in filament synthesis and their cognate chaperones are represented in italic colored font.
Figure 5
Figure 5
Bacterial flagellar filament proteins and their cognate specific chaperone form complexes with FlhA for filament exportation/synthesis. FliC and FliD proteins interact with each cognate chaperone FliS and FliT, respectively, before interacting with the cytosolic region of FlhA (FlhAC). Upper left—Cartoon representation of crystal structure 6CH2 (FlhAC-FliT-FliD complex from Salmonella enterica subsp. enterica serovar Typhimurium str. LT2. Upper right—Cartoon representation of crystal structure 6CH3 (FlhAC-FliS-FliC complex) from Salmonella enterica subsp. enterica serovar Typhimurium str. LT2). Lower left—Superposition of cartoon representation of both NMR solution structures: 5KRW (FliD-FliT) and 5KS6 (apo-FliT) from Salmonella enterica subsp. enterica serovar Typhimurium str. LT2. The FliT helix α4 is released upon FliD binding. Lower right—Cartoon representation of crystal structure 5MAW (FliS-FliC complex) from B. subtilis. Center figure—simplified schematic representation of the main flagellar components.
Figure 6
Figure 6
Flagellar filament, flagellin and FliD are implicated in various processes.
Figure 7
Figure 7
Flagellin recognition by the host. Extracellular detection—TLR5 receptor recognizes region on the D1 domain of flagellin and upon binding, TLR5 dimerizes starting a signaling cascade in the cytoplasm that leads to the alteration of gene expression; Intracellular detection (detected in mice only)—Naip 5 and 6 (NOD-like recpetors) rocognize C terminus of the flagellin. They recrute another NOD-like receptor NLRC4, which oligomerizes and activates caspase 1 forming a structure called inflammasome. Inflammasome activates molecules such as interleukins and gasdermin D leading to pyroptosis; Detection in plants—Plant receptor FLS2 recognizes N-terminal fragment of flagellin and upon binding FLS2 dimerizes with BAK1, protein kinase, starting a downstream signaling cascade that leads to the stomatal closure.
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