Abstract
Flagellum motility is critical for normal human development and for transmission of pathogenic protozoa that cause tremendous human suffering worldwide. Biophysical principles underlying motility of eukaryotic flagella are conserved from protists to vertebrates. However, individual cells exhibit diverse waveforms that depend on cell-specific elaborations on basic flagellum architecture. Trypanosoma brucei is a uniflagellated protozoan parasite that causes African sleeping sickness. The T. brucei flagellum is comprised of a 9+2 axoneme and an extra-axonemal paraflagellar rod (PFR), but the three-dimensional (3D) arrangement of the underlying structural units is poorly defined. Here, we use dual-axis electron tomography to determine the 3D architecture of the T. brucei flagellum. We define the T. brucei axonemal repeating unit. We observe direct connections between the PFR and axonemal dyneins, suggesting a mechanism by which mechanochemical signals may be transmitted from the PFR to axonemal dyneins. We find that the PFR itself is comprised of overlapping laths organized into distinct zones that are connected through twisting elements at the zonal interfaces. The overall structure has an underlying 57nm repeating unit. Biomechanical properties inferred from PFR structure lead us to propose that the PFR functions as a biomechanical spring that may store and transmit energy derived from axonemal beating. These findings provide insight into the structural foundations that underlie the distinctive flagellar waveform that is a hallmark of T. brucei cell motility.
Highlights
The eukaryotic flagellum is a biological machine that drives fluid movement across epithelial surfaces and propulsion of single cells
Flagellum motility is critical for normal human development and physiology, defects in motile and non-motile cilia cause a broad spectrum of human diseases, collectively referred to as ‘‘ciliopathies’’ [4,5]
The presence of paraflagellar rod (PFR) posed a limitation for frozenhydrated samples, as the PFR and axoneme lie side by side on the grid, restricting possible specimen orientations (Fig 1C)
Summary
The eukaryotic flagellum (synonymous with motile cilium) is a biological machine that drives fluid movement across epithelial surfaces and propulsion of single cells. Flagella are required for the motility of several important human pathogens that infect approximately 0.5 billion people worldwide [6,7]. Movement of these microbial pathogens through heterogeneous media, e.g. host blood and tissues, imposes particular demands on cell motility mechanisms [7,8] and their flagella exhibit characteristic, cell-specific beat forms [5,9,10]. Because the fundamental principles of axonemal motility are conserved, differences in beat form from one cell to another depend on cell-specific elaborations on flagellum architecture. Understanding structural foundations of flagellar motility has the potential to impact efforts to control and treat heritable and infectious disease in humans
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