Heterogeneity of radial spokes structural components and associated enzymes inTetrahymenacilia DOI Creative Commons
Marta Bicka, Avrin Ghanaeian, Corbin Black

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 12, 2023

Summary Radial spokes, RS1-RS2-RS3, are T-shaped, multiprotein complexes that transmit regulatory signals from central apparatus to outer doublet dyneins. RSs, especially RS3, differ in morphology, protein composition, and RS base-docked IDAs. Spokes defects alter cilia beating frequency, waveform, amplitude leading, humans, primary ciliary dyskinesia infertility. In contrast RS1 RS2, the composition of RS3 is partly resolved. Moreover, role particular spokes unclear. Ciliate Tetrahymena thermophila has three Rsp3 paralogs two or some other RSPs. Using multiple complementary approaches, we showed forms RS2 subtypes having core composed various one type Rsp3-less RS3. We elucidated proteomes identified novel RS-associated proteins, including enzymatic proteins involved local regulation ADP/ATP levels phosphorylation, whose presence further diversifies RSs properties likely functions. brief their architecture. Studies a ciliate revealed paralogs-dependent subtypes, diversity RSP3 mutants’ phenotype. Known components newly structural were assigned RSs.

Language: Английский

Structures of Native Doublet Microtubules from Trichomonas vaginalis Reveal Parasite-Specific Proteins as Potential Drug Targets DOI Creative Commons
Z. Hong Zhou, Alexander Stevens, S. K. Kashyap

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 2, 2024

Abstract Doublet microtubules (DMTs) are flagellar components required for the protist Trichomonas vaginalis (Tv) to swim through human genitourinary tract cause trichomoniasis, most common non-viral sexually transmitted disease. Lack of DMT structures has prevented structure-guided drug design manage Tv infection. Here, we determined cryo-EM structure native Tv-DMTs, identifying 29 unique proteins, including 18 microtubule inner proteins and 9 outer proteins. While A-tubule is simplistic compared DMTs other organisms, B-tubule features specialized, parasite-specific such as TvFAP40 TvFAP35 that form filaments near junctions, respectively, stabilize enable locomotion. Notably, a small molecule, assigned IP6, coordinated within pocket characteristics molecule. This first atomic model Tv-DMT highlights diversity eukaryotic motility machinery provides structural framework inform rational therapeutics.

Language: Английский

Citations

0
Structure of AcMNPV nucleocapsid reveals DNA portal organization and packaging apparatus of circular dsDNA baculovirus. DOI Creative Commons
Grégory Effantin, Eaazhisai Kandiah, Martin Pelosse

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

Abstract Baculoviruses are large DNA viruses found in nature propagating amongst insects and lepidoptera particular. Their viral cycle has been studied characterized over decades they nowadays considered as invaluable biotechnology tools widely used biopesticides, recombinant expression systems or delivery vehicle for gene therapy. However, very little is known about the baculovirus nucleocapsid assembly at a molecular level. Here, we solved whole structure of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) by applying cryo-electron microscopy (CryoEM) combined to de novo modelling Alphafold2 predictions. Our completes prior observations from helical sheath basal elucidate intricate architecture apical cap, unravelling first time organization baculoviral portal featuring intriguing symmetry mismatches between its core vertex. The core, closing capsid apex, holds two antiparallel helices covalently closed circular (ccc) genome tethered Ac54 proteins. Different components cap constituted same building block, made Ac101/Ac144, proving versatility this modular pair. crown forming vertex displays C21 contains, others, motor-like protein Ac66. findings support be involved packaging, most probably conjunction with other parts larger packaging apparatus that not bound mature virions await further elucidation.

Language: Английский

Citations

0
Heterogeneity of radial spokes structural components and associated enzymes inTetrahymenacilia DOI Creative Commons
Marta Bicka, Avrin Ghanaeian, Corbin Black

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 12, 2023

Summary Radial spokes, RS1-RS2-RS3, are T-shaped, multiprotein complexes that transmit regulatory signals from central apparatus to outer doublet dyneins. RSs, especially RS3, differ in morphology, protein composition, and RS base-docked IDAs. Spokes defects alter cilia beating frequency, waveform, amplitude leading, humans, primary ciliary dyskinesia infertility. In contrast RS1 RS2, the composition of RS3 is partly resolved. Moreover, role particular spokes unclear. Ciliate Tetrahymena thermophila has three Rsp3 paralogs two or some other RSPs. Using multiple complementary approaches, we showed forms RS2 subtypes having core composed various one type Rsp3-less RS3. We elucidated proteomes identified novel RS-associated proteins, including enzymatic proteins involved local regulation ADP/ATP levels phosphorylation, whose presence further diversifies RSs properties likely functions. brief their architecture. Studies a ciliate revealed paralogs-dependent subtypes, diversity RSP3 mutants’ phenotype. Known components newly structural were assigned RSs.

Language: Английский

Citations

0