Imperial College London

DrMorganBeeby

Faculty of Natural SciencesDepartment of Life Sciences

Reader in Structural Biology
 
 
 
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Contact

 

+44 (0)20 7594 5251m.beeby Website

 
 
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Location

 

502Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

75 results found

Kaplan M, Oikonomou CM, Wood CR, Chreifi G, Ghosal D, Dobro MJ, Yao Q, Pal RR, Baidya AK, Liu Y, Maggi S, McDowall AW, Ben-Yehuda S, Rosenshine I, Briegel A, Beeby M, Chang Y-W, Shaffer CL, Jensen GJet al., 2022, Discovery of a Novel Inner Membrane-Associated Bacterial Structure Related to the Flagellar Type III Secretion System, JOURNAL OF BACTERIOLOGY, Vol: 204, ISSN: 0021-9193

Journal article

Ortega D, Beeby M, 2022, How did the archaellum get its rotation?, Frontiers in Microbiology, Vol: 12, Pages: 1-6, ISSN: 1664-302X

How changes in function evolve fascinates many evolutionary biologists. Particularly captivating is the evolution of rotation in molecular machines, as it evokes familiar machines that we have made ourselves. The archaellum, an archaeal analog of the bacterial flagellum, is one of the simplest rotary motors. It features a long helical propeller attached to a cell envelope-embedded rotary motor. Satisfyingly, the archaellum is one of many members of the large type IV filament superfamily, which includes pili, secretion systems, and adhesins, relationships that promise clues as to how the rotating archaellum evolved from a non-rotary ancestor. Nevertheless,determining exactly how the archaellum got its rotation remains frustratingly elusive. Here we review what is known about how the archaellum got its rotation, what clues exist, and what more is needed to address this question.

Journal article

Kaplan M, Oikonomou CM, Wood CR, Chreifi G, Subramanian P, Ortega DR, Chang Y-W, Beeby M, Shaffer CL, Jensen GJet al., 2022, Novel transient cytoplasmic rings stabilize assembling bacterial flagellar motors, EMBO JOURNAL, Vol: 41, ISSN: 0261-4189

Journal article

Mandela E, Stubenrauch CJ, Ryoo D, Hwang H, Cohen EJ, Torres VL, Deo P, Webb CT, Huang C, Schittenhelm RB, Beeby M, Gumbart JC, Lithgow T, Hay IDet al., 2022, Adaptation of the periplasm to maintain spatial constraints essential for cell envelope processes and cell viability, ELIFE, Vol: 11, ISSN: 2050-084X

Journal article

Umrekar T, Winterborn Y, Sivabalasarma S, Brantl J, Albers S-V, Beeby Met al., 2021, Evolution of archaellum rotation involved invention of a stator complex by duplicating and modifying a core component, Frontiers in Microbiology, Vol: 12, Pages: 1-10, ISSN: 1664-302X

Novelty in biology can arise from opportunistic repurposing of nascent characteristics ofexisting features. Understanding how this process happens at the molecular scale, however,suffers from a lack of case studies. The evolutionary emergence of rotary motors is aparticularly clear example of evolution of a new function. The simplest of rotary motors is thearchaellum, a molecular motor that spins a helical propeller for archaeal motility analogous tothe bacterial flagellum. Curiously, emergence of archaellar rotation may have pivoted on thesimple duplication and repurposing of a pre-existing component to produce a stator complexthat anchors to the cell superstructure to enable productive rotation of the rotor component.This putative stator complex is composed of ArlF and ArlG, gene duplications of the filamentcomponent ArlB, providing an opportunity to study how gene duplication andneofunctionalization contributed to the radical innovation of rotary function. Towardunderstanding how this happened, we used electron cryomicroscopy to determine thestructure of isolated ArlG filaments, the major component of the stator complex. Using ahybrid modeling approach incorporating structure prediction and validation, we show thatArlG filaments are open helices distinct to the closed helical filaments of ArlB. Curiously,further analysis reveals that ArlG retains a subset of the inter-protomer interactions ofhomologous ArlB, resulting in a superficially different assembly that nevertheless reflects thecommon ancestry of the two structures. This relatively simple mechanism to changequaternary structure was likely associated with the evolutionary neofunctionalization of thearchaellar stator complex, and we speculate that the relative deformable elasticity of an openhelix may facilitate elastic energy storage during the transmission of the discrete bursts ofenergy released by ATP hydrolysis to continuous archaellar rotation, allowing the inherentproperties of a duplicated ArlB to be

Journal article

Ferreira JL, Coleman I, Addison ML, Zachs T, Quigley BL, Wuichet K, Beeby Met al., 2021, The "Jack-of-all-Trades" Flagellum From Salmonella and E. coli Was Horizontally Acquired From an Ancestral B-Proteobacterium (vol 12, 643180, 2021), FRONTIERS IN MICROBIOLOGY, Vol: 12

Journal article

Gumbart JC, Ferreira JL, Hwang H, Hazel AJ, Cooper CJ, Parks JM, Smith JC, Zgurskaya H, Beeby Met al., 2021, Lpp positions peptidoglycan at the AcrA-ToIC interface in the AcrAB-ToIC multidrug efflux pump, BIOPHYSICAL JOURNAL, Vol: 120, Pages: 3973-3982, ISSN: 0006-3495

Journal article

Kaplan M, Chreifi G, Metskas LA, Liedtke J, Wood CR, Oikonomou CM, Nicolas WJ, Subramanian P, Zacharoff LA, Wang Y, Chang Y-W, Beeby M, Dobro MJ, Zhu Y, McBride MJ, Briegel A, Shaffer CL, Jensen GJet al., 2021, In situ imaging of bacterial outer membrane projections and associated protein complexes using electron cryotomograpy, ELIFE, Vol: 10, ISSN: 2050-084X

Journal article

Matthews-Palmer T, Gonzalez-Rodriguez N, Calcraft T, Lagercrantz S, Zachs T, Yu X, Grabe G, Holden D, Nans A, Rosenthal P, Rouse S, Beeby Met al., 2021, Structure of the cytoplasmic domain of SctV (SsaV) from the Salmonella SPI-2 injectisome and implications for a pH sensing mechanism, Journal of Structural Biology, Vol: 213, ISSN: 1047-8477

Bacterial type III secretion systems assemble the axial structures of both injectisomes and flagella. Injectisome type III secretion systems subsequently secrete effector proteins through their hollow needle into a host, requiring co-ordination. In the Salmonella enterica serovar Typhimurium SPI-2 injectisome, this switch is triggered by sensing the neutral pH of the host cytoplasm. Central to specificity switching is a nonameric SctV protein with an N-terminal transmembrane domain and a toroidal C-terminal cytoplasmic domain. A ‘gatekeeper’ complex interacts with the SctV cytoplasmic domain in a pH dependent manner, facilitating translocon secretion while repressing effector secretion through a poorly understood mechanism. To better understand the role of SctV in SPI-2 translocon-effector specificity switching, we purified full-length SctV and determined its toroidal cytoplasmic region’s structure using cryo-EM. Structural comparisons and molecular dynamics simulations revealed that the cytoplasmic torus is stabilized by its core subdomain 3, about which subdomains 2 and 4 hinge, varying the flexible outside cleft implicated in gatekeeper and substrate binding. In light of patterns of surface conservation, deprotonation, and structural motion, the location of previously identified critical residues suggest that gatekeeper binds a cleft buried between neighboring subdomain 4s. Simulations suggest that a local pH change from 5 to 7.2 stabilizes the subdomain 3 hinge and narrows the central aperture of the nonameric torus. Our results are consistent with a model of local pH sensing at SctV, where pH-dependent dynamics of SctV cytoplasmic domain affect binding of gatekeeper complex.

Journal article

Kaplan M, Tocheva EI, Briegel A, Dobro MJ, Chang Y-W, Subramanian P, McDowall AW, Beeby M, Jensen GJet al., 2021, Loss of the Bacterial Flagellar Motor Switch Complex upon Cell Lysis, MBIO, Vol: 12, ISSN: 2150-7511

Journal article

Ferreira J, coleman I, Addison M, Zachs T, Quigley B, Wuichet K, Beeby Met al., 2021, The 'jack-of-all-trades' flagellum from Salmonella and E. coli was horizontally acquired from an ancestral beta-proteobacterium, Frontiers in Microbiology, Vol: 12, ISSN: 1664-302X

The γ-proteobacteria are a group of diverse bacteria including pathogenic Escherichia, Salmonella, Vibrio, and Pseudomonas species. The majority swim in liquids with polar, sodium-driven flagella and swarm on surfaces with lateral, non-chemotactic flagella. Notable exceptions are the enteric Enterobacteriaceae such as Salmonella and E. coli. Many of the well-studied Enterobacteriaceae are gut bacteria that both swim and swarm with the same proton-driven peritrichous flagella. How different flagella evolved in closely related lineages, however, has remained unclear. Here, we describe our phylogenetic finding that Enterobacteriaceae flagella are not native polar or lateral γ-proteobacterial flagella but were horizontally acquired from an ancestral β-proteobacterium. Using electron cryo-tomography and subtomogram averaging, we confirmed that Enterobacteriaceae flagellar motors resemble contemporary β-proteobacterial motors and are distinct to the polar and lateral motors of other γ-proteobacteria. Structural comparisons support a model in which γ-proteobacterial motors have specialized, suggesting that acquisition of a β-proteobacterial flagellum may have been beneficial as a general-purpose motor suitable for adjusting to diverse conditions. This acquisition may have played a role in the development of the enteric lifestyle.

Journal article

Sivabalasarma S, Wetzel H, Nussbaum P, van der Does C, Beeby M, Albers S-Vet al., 2021, Analysis of Cell-Cell Bridges in Haloferax volcanii Using Electron Cryo-Tomography Reveal a Continuous Cytoplasm and S-Layer, FRONTIERS IN MICROBIOLOGY, Vol: 11, ISSN: 1664-302X

Journal article

Umrekar TR, Cohen E, Drobnic T, Gonzalez-Rodriguez N, Beeby Met al., 2020, CryoEM of bacterial secretion systems: A primer for microbiologists, MOLECULAR MICROBIOLOGY, Vol: 115, Pages: 366-382, ISSN: 0950-382X

Journal article

Alvira S, Watkins DW, Troman L, Allen WJ, Lorriman JS, Degliesposti G, Cohen EJ, Beeby M, Daum B, Gold VAM, Skehel JM, Collinson Iet al., 2020, Inter-membrane association of the Sec and BAM translocons for bacterial outer-membrane biogenesis, ELIFE, Vol: 9, ISSN: 2050-084X

Journal article

Sivabalasarma S, Wetzel H, Nu├čbaum P, van der Does C, Beeby M, Albers S-Vet al., 2020, Analysis of cell-cell bridges in <i>Haloferax volcanii</i> using Electron cryo-tomography reveal a continuous cytoplasm and S-layer

<jats:p>Halophilic archaea exchange DNA and proteins using a fusion-based mating mechanism. Scanning electron microscopy previously suggested that mating involves an intermediate state, where cells are connected by an intercellular bridge. To better understand this process, we used electron cryotomography and fluorescence microscopy to visualize cells forming these intercellular bridges. Electron cryo-tomography showed that the observed bridges were enveloped by an S-layer and connected mating cells via a continuous cytoplasm. Macromolecular complexes like ribosomes and unknown thin filamentous helical structures were visualized in the cytoplasm inside the bridges, demonstrating that these bridges can facilitate exchange of cellular components. We followed formation of a cell-cell bridge by fluorescence time-lapse microscopy between cells at a distance of 1.5 µm. These results shed light on the process of haloarchaeal mating and highlight further mechanistic questions.</jats:p>

Journal article

de Llano E, Miao H, Ahmadi Y, Wilson AJ, Beeby M, Viola I, Barisic Iet al., 2020, Adenita: interactive 3D modelling and visualization of DNA nanostructures, NUCLEIC ACIDS RESEARCH, Vol: 48, Pages: 8269-8275, ISSN: 0305-1048

Journal article

Blagotinsek V, Schwan M, Steinchen W, Mrusek D, Hook JC, Rossmann F, Freibert SA, Kratzat H, Murat G, Kressler D, Beckmann R, Beeby M, Thormann KM, Bange Get al., 2020, An ATP-dependent partner switch links flagellar C-ring assembly with gene expression, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 117, Pages: 20826-20835, ISSN: 0027-8424

Journal article

Taylor PJ, Hagen J, Faruqu FN, Al-Jamal KT, Quigley B, Beeby M, Selkirk ME, Sarkies Pet al., 2020, Trichinella spiralis secretes abundant unencapsulated small RNAs with potential effects on host gene expression, International Journal for Parasitology, Vol: 50, Pages: 697-705, ISSN: 0020-7519

Many organisms, including parasitic nematodes, secrete small RNAs into the extracellular environment, largely encapsulated within small vesicles. Parasite-secreted material often contains microRNAs (miRNAs), raising the possibility that they might regulate host genes in target cells. Here we characterise secreted RNAs from the parasitic nematode Trichinella spiralis at two different life stages. We show that adult T. spiralis, which inhabit intestinal mucosa, secrete miRNAs within vesicles. Unexpectedly, T. spiralis muscle stage larvae, which live intracellularly within skeletal muscle cells, secrete miRNAs that appear not to be encapsulated. Notably, secreted miRNAs include a homologue of mammalian miRNA-31, which has an important role in muscle development. Our work therefore suggests that RNAs may be secreted without encapsulation in vesicles, with implications for the biology of T. spiralis infection.

Journal article

Cohen EJ, Nakane D, Kabata Y, Hendrixson DR, Nishizaka T, Beeby Met al., 2020, Campylobacter jejuni motility integrates specialized cell shape, flagellar filament, and motor, to coordinate action of its opposed flagella, PLoS Pathogens, Vol: 16, Pages: 1-24, ISSN: 1553-7366

Campylobacter jejuni rotates a flagellum at each pole to swim through the viscous mucosa of its hosts’ gastrointestinal tracts. Despite their importance for host colonization, however, how C. jejuni coordinates rotation of these two opposing flagella is unclear. As well as their polar placement, C. jejuni’s flagella deviate from the norm of Enterobacteriaceae in other ways: their flagellar motors produce much higher torque and their flagellar filament is made of two different zones of two different flagellins. To understand how C. jejuni’s opposed motors coordinate, and what contribution these factors play in C. jejuni motility, we developed strains with flagella that could be fluorescently labeled, and observed them by high-speed video microscopy. We found that C. jejuni coordinates its dual flagella by wrapping the leading filament around the cell body during swimming in high-viscosity media and that its differentiated flagellar filament and helical body have evolved to facilitate this wrapped-mode swimming.

Journal article

Cohen EJ, Nakane D, Kabata Y, Hendrixson DR, Nishizaka T, Beeby Met al., 2020, Campylobacter jejunimotility integrates specialized cell shape, flagellar filament, and motor, to coordinate action of its opposed flagella, PLoS Pathogens, Vol: 16, Pages: 1-24, ISSN: 1553-7366

Campylobacter jejuni rotates a flagellum at each pole to swim through the viscous mucosa of its hosts’ gastrointestinal tracts. Despite their importance for host colonization, however, how C. jejuni coordinates rotation of these two opposing flagella is unclear. As well as their polar placement, C. jejuni’s flagella deviate from the norm of Enterobacteriaceae in other ways: their flagellar motors produce much higher torque and their flagellar filament is made of two different zones of two different flagellins. To understand how C. jejuni’s opposed motors coordinate, and what contribution these factors play in C. jejuni motility, we developed strains with flagella that could be fluorescently labeled, and observed them by high-speed video microscopy. We found that C. jejuni coordinates its dual flagella by wrapping the leading filament around the cell body during swimming in high-viscosity media and that its differentiated flagellar filament and helical body have evolved to facilitate this wrapped-mode swimming.

Journal article

Beeby M, 2020, Toward Organism-scale Structural Biology: S-layer Reined in by Bacterial LPS, TRENDS IN BIOCHEMICAL SCIENCES, Vol: 45, Pages: 549-551, ISSN: 0968-0004

Journal article

Rossmann F, Hug I, Sangermani M, Jenal U, Beeby Met al., 2020, In situ structure of the Caulobacter crescentus flagellar motor and visualization of binding of a CheY-homolog, Molecular Microbiology, ISSN: 0950-382X

Journal article

Ahmadi Y, Nord AL, Wilson AJ, Huetter C, Schroeder F, Beeby M, Barisic Iet al., 2020, The Brownian and Flow-Driven Rotational Dynamics of a Multicomponent DNA Origami-Based Rotor, SMALL, Vol: 16, ISSN: 1613-6810

Journal article

Beeby M, Ferreira J, Tripp P, Albers S-V, Mitchell Det al., 2020, Propulsive nanomachines: the convergent evolution of archaella, flagella, and cilia, FEMS Microbiology Reviews, Vol: 44, Pages: 253-304, ISSN: 0168-6445

Echoing the repeated convergent evolution of flight and vision in large eukaryotes, propulsive swimming motility has evolved independently in microbes in each of the three domains of life. Filamentous appendages—archaella in Archaea, flagella in Bacteria, and cilia in Eukaryotes—wave, whip, or rotate to propel microbes, overcoming diffusion and enabling colonization of new environments. The implementations of the three propulsive nanomachines are distinct, however: archaella and flagella rotate, while cilia beat or wave; flagella and cilia assemble at their tips, while archaella assemble at their base; archaella and cilia use ATP for motility, while flagella use ion-motive force. These underlying differences reflect the tinkering required to evolve a propulsive molecular machine, in which pre-existing machines in the appropriate contexts were iteratively co-opted for new functions, and whose origins are reflected in the resultant mechanisms. Contemporary homologies suggest that archaella evolved from a non-rotary pilus, flagella from a non-rotary appendage or secretion system, and cilia from a passive sensory structure. Here we review the structure, assembly, mechanism, and homologies of the three distinct solutions as a foundation to better understand how propulsive nanomachines evolved three times independently and to highlight principles of molecular evolution.

Journal article

Kaplan M, Sweredoski MJ, Rodrigues JPGLM, Tocheva EI, Chang Y-W, Ortega DR, Beeby M, Jensen GJet al., 2020, Bacterial flagellar motor PL-ring disassembly subcomplexes are widespread and ancient, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 117, Pages: 8941-8947, ISSN: 0027-8424

Journal article

Taylor P, Hagen J, Faruqu F, Al-Jamal K, Quigley B, Beeby M, Selkirk M, Sarkies Pet al., 2020, Trichinella spiralis secretes abundant unencapsulated small RNAs with potential effects on host gene expression, Publisher: bioRxiv

Abstract Many organisms, including parasitic nematodes, secrete small RNAs into the extracellular environment largely encapsulated within small vesicles. Parasite secreted material often contains microRNAs (miRNAs), raising the possibility that they might contribute to pathology by regulating host genes in target cells. Here we characterise material from the parasitic nematode Trichinella spiralis at two different life stages. We show that adult T. spiralis , which inhabit intestinal mucosa, secrete miRNAs within vesicles. Unexpectedly however, T. spiralis muscle stage larvae (MSL), which live intracellularly within skeletal muscle cells, secrete miRNAs that appear not to be encapsulated. Notably, secreted miRNAs include a homologue of mammalian miRNA-31, which has an important role in muscle development. Our work therefore suggests a new potential mechanism of RNA secretion with implications for the pathology of T. spiralis infection.

Working paper

Gumbart JC, Ferreira J, Hwang S, Hazel A, Parks JM, Smith JC, Beeby M, Zgurskaya Het al., 2020, Modeling the Placement of the AcrAB-TolC Multidrug Efflux Pump in the Bacterial Cell Envelope, 64th Annual Meeting of the Biophysical-Society, Publisher: CELL PRESS, Pages: 13A-13A, ISSN: 0006-3495

Conference paper

Henderson LD, Matthews-Palmer TRS, Gulbronson CJ, Ribardo DA, Beeby M, Hendrixson DRet al., 2020, Diversification of campylobacter jejuni flagellar C-Ring composition impacts its structure and function in motility, flagellar assembly, and cellular processes., mBio, Vol: 11, Pages: 1-21, ISSN: 2150-7511

Bacterial flagella are reversible rotary motors that rotate external filaments for bacterial propulsion. Some flagellar motors have diversified by recruiting additional components that influence torque and rotation, but little is known about the possible diversification and evolution of core motor components. The mechanistic core of flagella is the cytoplasmic C ring, which functions as a rotor, directional switch, and assembly platform for the flagellar type III secretion system (fT3SS) ATPase. The C ring is composed of a ring of FliG proteins and a helical ring of surface presentation of antigen (SPOA) domains from the switch proteins FliM and one of two usually mutually exclusive paralogs, FliN or FliY. We investigated the composition, architecture, and function of the C ring of Campylobacter jejuni, which encodes FliG, FliM, and both FliY and FliN by a variety of interrogative approaches. We discovered a diversified C. jejuni C ring containing FliG, FliM, and both FliY, which functions as a classical FliN-like protein for flagellar assembly, and FliN, which has neofunctionalized into a structural role. Specific protein interactions drive the formation of a more complex heterooligomeric C. jejuni C-ring structure. We discovered that this complex C ring has additional cellular functions in polarly localizing FlhG for numerical regulation of flagellar biogenesis and spatial regulation of division. Furthermore, mutation of the C. jejuni C ring revealed a T3SS that was less dependent on its ATPase complex for assembly than were other systems. Our results highlight considerable evolved flagellar diversity that impacts motor output, biogenesis, and cellular processes in different species.IMPORTANCE The conserved core of bacterial flagellar motors reflects a shared evolutionary history that preserves the mechanisms essential for flagellar assembly, rotation, and directional switching. In this work, we describe an expanded and diversified set of core components in the Ca

Journal article

Tsai C-L, Tripp P, Sivabalasarma S, Zhang C, Rodriguez-Franco M, Wipfler RL, Chaudhury P, Banerjee A, Beeby M, Whitaker RJ, Tainer JA, Albers S-Vet al., 2020, The structure of the periplasmic FlaG-FlaF complex and its essential role for archaellar swimming motility, NATURE MICROBIOLOGY, Vol: 5, Pages: 216-225, ISSN: 2058-5276

Journal article

Cohen EJ, Nakane D, Kabata Y, Hendrixson DR, Nishizaka T, Beeby Met al., 2019, “<i>Campylobacter jejuni</i>motility integrates specialized cell shape, flagellar filament, and motor, to coordinate action of its opposed flagella in viscous media”

<jats:title>Abstract</jats:title><jats:p><jats:italic>Campylobacter jejuni</jats:italic>rotates a flagellum at each pole to swim through the viscous mucosa of its hosts’ gastrointestinal tracts. Despite their importance for host colonization, however, how<jats:italic>C. jejuni</jats:italic>coordinates rotation of these two opposing flagella is unclear. As well as their polar placement,<jats:italic>C. jejuni’s</jats:italic>flagella deviate from the Enterobacteriaceael norm in other ways: their flagellar motors produce much higher torque and their flagellar filament is made of two different zones of two different flagellins. To understand how<jats:italic>C. jejuni’s</jats:italic>opposed motors coordinate, and what contribution these factors play in<jats:italic>C. jejuni</jats:italic>motility, we developed strains with flagella that could be fluorescently labeled, and observed them by high-speed video microscopy. We found that<jats:italic>C. jejuni</jats:italic>coordinates its dual flagella by wrapping the leading filament around the cell body during swimming in high-viscosity media and that its differentiated flagellar filament has evolved to facilitate this wrapped-mode swimming. Unexpectedly,<jats:italic>C. jejuni</jats:italic>’s helical body is important for facile unwrapping of the flagellar filament from the cell body during switching of swimming trajectory. Our findings demonstrate how multiple facets of<jats:italic>C. jejuni’s</jats:italic>flagella and cell plan have co-evolved for optimal motility in high-viscosity environments.</jats:p>

Journal article

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