Oxford Molecular Motors

Abstract:

We study the large-scale anisotropy of the universe by measuring the dipole in the angular distribution of a flux-limited, all-sky sample of 1.36 million quasars observed by the Wide-field Infrared Survey Explorer (WISE). This sample is derived from the new CatWISE2020 catalog, which contains deep photometric measurements at 3.4 and 4.6 μm from the cryogenic, post-cryogenic, and reactivation phases of the WISE mission. While the direction of the dipole in the quasar sky is similar to that of the cosmic microwave background (CMB), its amplitude is over twice as large as expected, rejecting the canonical, exclusively kinematic interpretation of the CMB dipole with a p-value of 5 × 10−7 (4.9σ for a normal distribution, one-sided), the highest significance achieved to date in such studies. Our results are in conflict with the cosmological principle, a foundational assumption of the concordance ΛCDM model.

Abstract:

Regulatory switches are wide spread in many biological systems. Uniquely among them, the switch of the bacterial flagellar motor is not an on/off switch but rather controls the motor's direction of rotation in response to binding of the signaling protein CheY. Despite its extensive study, the molecular mechanism underlying this switch has remained largely unclear. Here, we resolved the functions of each of the three CheY-binding sites at the switch in E. coli, as well as their different dependencies on phosphorylation and acetylation of CheY. Based on this, we propose that CheY motor switching activity is potentiated upon binding to the first site. Binding of potentiated CheY to the second site produces unstable switching and at the same time enables CheY binding to the third site, an event that stabilizes the switched state. Thereby, this mechanism exemplifies a unique combination of tight motor regulation with inherent switching flexibility.

Abstract:

Archaea swim using the archaellum (archaeal flagellum), a reversible rotary motor consisting of a torque-generating motor and a helical filament, which acts as a propeller. Unlike the bacterial flagellar motor (BFM), ATP (adenosine-5′-triphosphate) hydrolysis probably drives both motor rotation and filamentous assembly in the archaellum. However, direct evidence is still lacking due to the lack of a versatile model system. Here, we present a membrane-permeabilized ghost system that enables the manipulation of intracellular contents, analogous to the triton model in eukaryotic flagella and gliding Mycoplasma. We observed high nucleotide selectivity for ATP driving motor rotation, negative cooperativity in ATP hydrolysis, and the energetic requirement for at least 12 ATP molecules to be hydrolyzed per revolution of the motor. The response regulator CheY increased motor switching from counterclockwise (CCW) to clockwise (CW) rotation. Finally, we constructed the torque–speed curve at various [ATP]s and discuss rotary models in which the archaellum has characteristics of both the BFM and F1-ATPase. Because archaea share similar cell division and chemotaxis machinery with other domains of life, our ghost model will be an important tool for the exploration of the universality, diversity, and evolution of biomolecular machinery.