资源环境科技发展态势分析平台

Microtubules are dynamic polymers of alpha- and beta-tubulin and have crucial roles in cell signalling, cell migration, intracellular transport and chromosome segregation(1). They assemble de novo from alpha beta-tubulin dimers in an essential process termed microtubule nucleation. Complexes that contain the protein gamma-tubulin serve as structural templates for the microtubule nucleation reaction(2). In vertebrates, microtubules are nucleated by the 2.2-megadalton gamma-tubulin ring complex (gamma-TuRC), which comprises gamma-tubulin, five related gamma-tubulin complex proteins (GCP2-GCP6) and additional factors(3). GCP6 is unique among the GCP proteins because it carries an extended insertion domain of unknown function. Our understanding of microtubule formation in cells and tissues is limited by a lack of high-resolution structural information on the gamma-TuRC. Here we present the cryo-electron microscopy structure of gamma-TuRC from Xenopus laevis at 4.8 angstrom global resolution, and identify a 14-spoked arrangement of GCP proteins and gamma-tubulins in a partially flexible open left-handed spiral with a uniform sequence of GCP variants. By forming specific interactions with other GCP proteins, the GCP6-specific insertion domain acts as a scaffold for the assembly of the gamma-TuRC. Unexpectedly, we identify actin as a bona fide structural component of the gamma-TuRC with functional relevance in microtubule nucleation. The spiral geometry of gamma-TuRC is suboptimal for microtubule nucleation and a controlled conformational rearrangement of the gamma-TuRC is required for its activation. Collectively, our cryo-electron microscopy reconstructions provide detailed insights into the molecular organization, assembly and activation mechanism of vertebrate gamma-TuRC, and will serve as a framework for the mechanistic understanding of fundamental biological processes associated with microtubule nucleation, such as meiotic and mitotic spindle formation and centriole biogenesis(4).

The cryo-EM structure of the gamma-tubulin ring complex (gamma-TuRC) from Xenopus laevis provides insights into the molecular organization of the complex, and shows that actin is a structural component that is functionally relevant to microtubule nucleation.

A neuromodulator produced by commensalProvidenciabacteria that colonize the gut ofCaenorhabditis elegansmimics the functions of the cognate host molecule to manipulate a sensory decision of the host.

Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms(1). Some bacteria produce bioactive neurotransmitters that have previously been proposed to modulate nervous system activity and behaviours of their hosts(2,3). However, the mechanistic basis of this microbiota-brain signalling and its physiological relevance are largely unknown. Here we show that inCaenorhabditis elegans, the neuromodulator tyramine produced by commensalProvidenciabacteria, which colonize the gut, bypasses the requirement for host tyramine biosynthesis and manipulates a host sensory decision. Bacterially produced tyramine is probably converted to octopamine by the host tyramine beta-hydroxylase enzyme. Octopamine, in turn, targets the OCTR-1 octopamine receptor on ASH nociceptive neurons to modulate an aversive olfactory response. We identify the genes that are required for tyramine biosynthesis inProvidencia, and show that these genes are necessary for the modulation of host behaviour. We further find thatC. eleganscolonized byProvidenciapreferentially select these bacteria in food choice assays, and that this selection bias requires bacterially produced tyramine and host octopamine signalling. Our results demonstrate that a neurotransmitter produced by gut bacteria mimics the functions of the cognate host molecule to override host control of a sensory decision, and thereby promotes fitness of both the host and the microorganism.

The discovery of superconductivity at 200 kelvin in the hydrogen sulfide system at high pressures(1) demonstrated the potential of hydrogen-rich materials as high-temperature superconductors. Recent theoretical predictions of rare-earth hydrides with hydrogen cages(2,3) and the subsequent synthesis of LaH10 with a superconducting critical temperature (T-c) of 250 kelvin(4,5) have placed these materials on the verge of achieving the long-standing goal of room-temperature superconductivity. Electrical and X-ray diffraction measurements have revealed a weakly pressure-dependent T-c for LaH10 between 137 and 218 gigapascals in a structure that has a face-centred cubic arrangement of lanthanum atoms(5). Here we show that quantum atomic fluctuations stabilize a highly symmetrical Fm (3) over barm crystal structure over this pressure range. The structure is consistent with experimental findings and has a very large electron-phonon coupling constant of 3.5. Although ab initio classical calculations predict that this Fm (3) over barm structure undergoes distortion at pressures below 230 gigapascals(2,3,) yielding a complex energy landscape, the inclusion of quantum effects suggests that it is the true ground-state structure. The agreement between the calculated and experimental Tc values further indicates that this phase is responsible for the superconductivity observed at 250 kelvin. The relevance of quantum fluctuations calls into question many of the crystal structure predictions that have been made for hydrides within a classical approach and that currently guide the experimental quest for room-temperature superconductivity(6-8). Furthermore, we find that quantum effects are crucial for the stabilization of solids with high electron-phonon coupling constants that could otherwise be destabilized by the large electron-phonon interaction(9), thus reducing the pressures required for their synthesis.