Structural morphing in a symmetry-mismatched viral vertex

Fang, Qianglin; Tang, Wei-Chun; Mahalingam, Marthandan; Fokine, Andrei; Rossmann, Michael G.; Rao, Venigalla B.

doi:10.1038/s41467-020-15575-4

Cited by 32 publications

(48 citation statements)

References 72 publications

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“…Structural details of PFR connections to the axoneme provide insight into how the PFR may influence axoneme beating. The mismatch in periodicity of the axoneme (8 nm) and the PFR (54 nm) is reminiscent of symmetry mismatch often observed in structures involved in dynamic biological processes, such as those of the DNA translocation portals in viruses 77 , 78 . Dynamic interaction is also supported by the observed heterogeneity in spacing of the PAC7–DMT7 interface (Fig.…”

Section: Discussionmentioning

confidence: 98%

Structure of the trypanosome paraflagellar rod and insights into non-planar motility of eukaryotic cells

et al. 2021

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Eukaryotic flagella (synonymous with cilia) rely on a microtubule-based axoneme, together with accessory filaments to carryout motility and signaling functions. While axoneme structures are well characterized, 3D ultrastructure of accessory filaments and their axoneme interface are mostly unknown, presenting a critical gap in understanding structural foundations of eukaryotic flagella. In the flagellum of the protozoan parasite Trypanosoma brucei (T. brucei), the axoneme is accompanied by a paraflagellar rod (PFR) that supports non-planar motility and signaling necessary for disease transmission and pathogenesis. Here, we employed cryogenic electron tomography (cryoET) with sub-tomographic averaging, to obtain structures of the PFR, PFR-axoneme connectors (PACs), and the axonemal central pair complex (CPC). The structures resolve how the 8 nm repeat of the axonemal tubulin dimer interfaces with the 54 nm repeat of the PFR, which consist of proximal, intermediate, and distal zones. In the distal zone, stacked “density scissors” connect with one another to form a “scissors stack network (SSN)” plane oriented 45° to the axoneme axis; and ~370 parallel SSN planes are connected by helix-rich wires into a paracrystalline array with ~90% empty space. Connections from these wires to the intermediate zone, then to overlapping layers of the proximal zone and to the PACs, and ultimately to the CPC, point to a contiguous pathway for signal transmission. Together, our findings provide insights into flagellum-driven, non-planar helical motility of T. brucei and have broad implications ranging from cell motility and tensegrity in biology, to engineering principles in bionics.

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Section: Discussionmentioning

confidence: 98%

Structure of the trypanosome paraflagellar rod and insights into non-planar motility of eukaryotic cells

et al. 2021

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“…The motor subunits must be flexible enough to adjust and generate this asymmetric “nucleosome-like” structure; the helical organization is also expected to lead to different motor subunits binding DNA with different strengths. The asymmetric interactions at the symmetry-mismatched portal vertex, a conserved feature in phages and viruses, would also impart additional flexibility to attain this configuration (33, 34). Consequently, one of the motor subunits (#1) binds DNA with the largest affinity and the rest in decreasing order with subunit #5 with the least affinity due to the expected strain on the binding elements.…”

Section: Discussionmentioning

confidence: 99%

A viral genome packaging ring-ATPase is a flexibly coordinated pentamer

Dai

Singh

et al. 2021

Preprint

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Multi-subunit ring-ATPases carry out a myriad of biological functions, including genome packaging in viruses. Though the basic structures and functions of these motors have been well-established, the mechanisms of ATPase firing and motor coordination are poorly understood. Here, by direct counting using single-molecule fluorescence, we have determined that the active bacteriophage T4 DNA packaging motor consists of five subunits of gp17. By systematically doping motors with an ATPase-defective subunit and selecting single motors containing a precise count of active/inactive subunit(s), we found, unexpectedly, that the packaging motor can tolerate an inactive subunit. However, motors containing an inactive subunit(s) exhibit fewer DNA engagements, a higher failure rate in encapsidation, reduced packaging velocity, and increased pausing. These findings suggest a new packaging model in which the motor, by re-adjusting its grip on DNA, can skip an inactive subunit and resume DNA translocation, contrary to the prevailing notion of strict coordination amongst motor subunits of other packaging motors.

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“…Nevertheless, it is not clear if any of these systems rotate, or whether they benefit from rotation if they do. Indeed, phages have now been shown not to rotate (Hugel et al, 2007), and feature sophisticated inter‐symmetry interfaces that prevent interface slippage (Fang et al, 2020). Symmetry mismatch may be inevitable in cylindrical multiprotein complexes built of disparate cyclic or helical oligomers, with selective pressure driving evolution of assemblies that can cope with symmetry mismatch instead of driving evolution of proteins that all assemble with the same symmetry.…”

Section: Discussionmentioning

confidence: 99%

Section: Con Clus Ionsmentioning

confidence: 99%

CryoEM of bacterial secretion systems: A primer for microbiologists

Umrekar

Cohen

Drobnič

et al. 2020

Molecular Microbiology

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Bacterial secretion systems all tackle the challenge of secreting substrates from the cytoplasm out of the cell. Many unrelated secretion systems have evolved, strikingly diverse in their structures and mechanisms, from the small pump-like type II secretion systems to the colossal harpoon-like type VI secretion systems. What makes secretion systems intriguing also makes them difficult to study, however: they are cell envelope-associated, frequently contain moving or transiently associated components, and are very large.Cryogenic electron microscopy (CryoEM) is ideally poised to study secretion systems. CryoEM excels at determining the structures of large protein complexes, can discern different conformational states, and can image structures in situ. CryoEM has come of age in the past half-decade following a spectacular resolution revolution that changed cryoEM from low-resolution "blobology" to a methodology that can compete with X-ray crystallography and NMR for structure determination of biological molecules (Kühlbrandt, 2014). Here, we provide a primer for microbiologists on these capabilities. We describe its basic principles, its two main forms, and what the two forms can and cannot achieve. We then highlight the contributions of cryoEM to understanding how the diverse microbial secretion systems work, focusing on type III secretion systems. We end with a forward-facing overview of future prospects. | Cr yoEMCryoEM is a family of techniques that determine the three-dimensional (3-D) structures of biological molecules from two-dimensional (2-D) electron micrographs. In basic terms, this is achieved by imaging the specimen from many different angles to facilitate piecing together

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Structural morphing in a symmetry-mismatched viral vertex

Cited by 32 publications

References 72 publications

Structure of the trypanosome paraflagellar rod and insights into non-planar motility of eukaryotic cells

Structure of the trypanosome paraflagellar rod and insights into non-planar motility of eukaryotic cells

A viral genome packaging ring-ATPase is a flexibly coordinated pentamer

CryoEM of bacterial secretion systems: A primer for microbiologists

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