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Insights into the assembly and activation of the microtubule nucleator gamma-TuRC 期刊论文
NATURE, 2020, 578 (7795) : 467-+
作者:  Cyranoski, David
收藏  |  浏览/下载:16/0  |  提交时间:2020/07/03

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.


  
Proton-assisted growth of ultra-flat graphene films 期刊论文
NATURE, 2020, 577 (7789) : 204-+
作者:  Yuan, Guowen;  Lin, Dongjing;  Wang, Yong;  Huang, Xianlei;  Chen, Wang;  Xie, Xuedong;  Zong, Junyu;  Yuan, Qian-Qian;  Zheng, Hang;  Wang, Di;  Xu, Jie;  Li, Shao-Chun;  Zhang, Yi;  Sun, Jian;  Xi, Xiaoxiang;  Gao, Libo
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/03

Graphene films grown by chemical vapour deposition have unusual physical and chemical properties that offer promise for applications such as flexible electronics and high-frequency transistors(1-10). However, wrinkles invariably form during growth because of the strong coupling to the substrate, and these limit the large-scale homogeneity of the film(1-4,11,12). Here we develop a proton-assisted method of chemical vapour deposition to grow ultra-flat graphene films that are wrinkle-free. Our method of proton penetration(13-17) and recombination to form hydrogen can also reduce the wrinkles formed during traditional chemical vapour deposition of graphene. Some of the wrinkles disappear entirely, owing to the decoupling of van der Waals interactions and possibly an increase in distance from the growth surface. The electronic band structure of the as-grown graphene films shows a V-shaped Dirac cone and a linear dispersion relation within the atomic plane or across an atomic step, confirming the decoupling from the substrate. The ultra-flat nature of the graphene films ensures that their surfaces are easy to clean after a wet transfer process. A robust quantum Hall effect appears even at room temperature in a device with a linewidth of 100 micrometres. Graphene films grown by proton-assisted chemical vapour deposition should largely retain their intrinsic performance, and our method should be easily generalizable to other nanomaterials for strain and doping engineering.


  
Single-chain heteropolymers transport protons selectively and rapidly 期刊论文
NATURE, 2020, 577 (7789) : 216-+
作者:  Jiang, Tao;  Hall, Aaron;  Eres, Marco;  Hemmatian, Zahra;  Qiao, Baofu;  Zhou, Yun;  Ruan, Zhiyuan;  Couse, Andrew D.;  Heller, William T.;  Huang, Haiyan;  de la Cruz, Monica Olvera;  Rolandi, Marco;  Xu, Ting
收藏  |  浏览/下载:9/0  |  提交时间:2020/07/03

Precise protein sequencing and folding are believed to generate the structure and chemical diversity of natural channels(1,2), both of which are essential to synthetically achieve proton transport performance comparable to that seen in natural systems. Geometrically defined channels have been fabricated using peptides, DNAs, carbon nanotubes, sequence-defined polymers and organic frameworks(3-13). However, none of these channels rivals the performance observed in their natural counterparts. Here we show that without forming an atomically structured channel, four-monomer-based random heteropolymers (RHPs)(14) can mimic membrane proteins and exhibit selective proton transport across lipid bilayers at a rate similar to those of natural proton channels. Statistical control over the monomer distribution in an RHP leads to segmental heterogeneity in hydrophobicity, which facilitates the insertion of single RHPs into the lipid bilayers. It also results in bilayer-spanning segments containing polar monomers that promote the formation of hydrogen-bonded chains(15,16) for proton transport. Our study demonstrates the importance of the adaptability that is enabled by statistical similarity among RHP chains and of the modularity provided by the chemical diversity of monomers, to achieve uniform behaviour in heterogeneous systems. Our results also validate statistical randomness as an unexplored approach to realize protein-like behaviour at the single-polymer-chain level in a predictable manner.


  
Localization and delocalization of light in photonic moire lattices 期刊论文
NATURE, 2020, 577 (7788) : 42-+
作者:  Wang, Peng;  Zheng, Yuanlin;  Chen, Xianfeng;  Huang, Changming;  Kartashov, Yaroslav V.;  Torner, Lluis;  Konotop, Vladimir V.;  Ye, Fangwei
收藏  |  浏览/下载:12/0  |  提交时间:2020/07/03

Moire lattices consist of two superimposed identical periodic structures with a relative rotation angle. Moire lattices have several applications in everyday life, including artistic design, the textile industry, architecture, image processing, metrology and interferometry. For scientific studies, they have been produced using coupled graphene-hexagonal boron nitride monolayers(1,2), graphene-graphene layers(3,4) and graphene quasicrystals on a silicon carbide surface(5). The recent surge of interest in moire lattices arises from the possibility of exploring many salient physical phenomena in such systems  examples include commensurable-incommensurable transitions and topological defects(2), the emergence of insulating states owing to band flattening(3,6), unconventional superconductivity(4) controlled by the rotation angle(7,8), the quantum Hall effect(9), the realization of non-Abelian gauge potentials(10) and the appearance of quasicrystals at special rotation angles(11). A fundamental question that remains unexplored concerns the evolution of waves in the potentials defined by moire lattices. Here we experimentally create two-dimensional photonic moire lattices, which-unlike their material counterparts-have readily controllable parameters and symmetry, allowing us to explore transitions between structures with fundamentally different geometries (periodic, general aperiodic and quasicrystal). We observe localization of light in deterministic linear lattices that is based on flatband physics(6), in contrast to previous schemes based on light diffusion in optical quasicrystals(12), where disorder is required(13) for the onset of Anderson localization(14) (that is, wave localization in random media). Using commensurable and incommensurable moire patterns, we experimentally demonstrate the twodimensional localization-delocalization transition of light. Moire lattices may feature an almost arbitrary geometry that is consistent with the crystallographic symmetry groups of the sublattices, and therefore afford a powerful tool for controlling the properties of light patterns and exploring the physics of periodic-aperiodic phase transitions and two-dimensional wavepacket phenomena relevant to several areas of science, including optics, acoustics, condensed matter and atomic physics.


  
Structure and mechanism of the mitochondrial Ca2+ uniporter holocomplex 期刊论文
NATURE, 2020
作者:  Kalaany, Nada Y.;  Sabatini, David M.
收藏  |  浏览/下载:21/0  |  提交时间:2020/07/03

Mitochondria take up Ca2+ through the mitochondrial calcium uniporter complex to regulate energy production, cytosolic Ca2+ signalling and cell death(1,2). In mammals, the uniporter complex (uniplex) contains four core components: the pore-forming MCU protein, the gatekeepers MICU1 and MICU2, and an auxiliary subunit, EMRE, essential for Ca2+ transport(3-8). To prevent detrimental Ca2+ overload, the activity of MCU must be tightly regulated by MICUs, which sense changes in cytosolic Ca2+ concentrations to switch MCU on and off(9,10). Here we report cryo-electron microscopic structures of the human mitochondrial calcium uniporter holocomplex in inhibited and Ca2+-activated states. These structures define the architecture of this multicomponent Ca2+-uptake machinery and reveal the gating mechanism by which MICUs control uniporter activity. Our work provides a framework for understanding regulated Ca2+ uptake in mitochondria, and could suggest ways of modulating uniporter activity to treat diseases related to mitochondrial Ca2+ overload.


Cryo-electron microscopy reveals the structures of the mitochondrial calcium uniporter holocomplex in low- and high-calcium conditions, showing the gating mechanism that underlies uniporter activation in response to intracellular calcium signals.


  
Extreme rainfall triggered the 2018 rift eruption at Kilauea Volcano 期刊论文
NATURE, 2020, 580 (7804) : 491-+
作者:  Cloutier, Richard;  Clement, Alice M.;  Lee, Michael S. Y.;  Noel, Roxanne;  Bechard, Isabelle;  Roy, Vincent;  Long, John A.
收藏  |  浏览/下载:33/0  |  提交时间:2020/05/13

The May 2018 rift intrusion and eruption of Kilauea Volcano, Hawai'  i, represented one of its most extraordinary eruptive sequences in at least 200 years, yet the trigger mechanism remains elusive(1). The event was preceded by several months of anomalously high precipitation. It has been proposed that rainfall can modulate shallow volcanic activity(2,3), but it remains unknown whether it can have impacts at the greater depths associated with magma transport. Here we show that immediately before and during the eruption, infiltration of rainfall into Kilauea Volcano'  s subsurface increased pore pressure at depths of 1 to 3 kilometres by 0.1 to 1 kilopascals, to its highest pressure in almost 50 years. We propose that weakening and mechanical failure of the edifice was driven by changes in pore pressure within the rift zone, prompting opportunistic dyke intrusion and ultimately facilitating the eruption. A precipitation-induced eruption trigger is consistent with the lack of precursory summit inflation, showing that this intrusion-unlike others-was not caused by the forceful intrusion of new magma into the rift zone. Moreover, statistical analysis of historic eruption occurrence suggests that rainfall patterns contribute substantially to the timing and frequency of Kilauea'  s eruptions and intrusions. Thus, volcanic activity can be modulated by extreme rainfall triggering edifice rock failure-a factor that should be considered when assessing volcanic hazards. Notably, the increasingly extreme weather patterns associated with ongoing anthropogenic climate change could increase the potential for rainfall-triggered volcanic phenomena worldwide.


Immediately before and during the eruption of Ki & x304  lauea Volcano in May 2018, anomalously high rainfall increased the pore pressure in the subsurface to its highest level in 50 years, causing weakening and mechanical failure of the edifice.


  
Femtosecond-to-millisecond structural changes in a light-driven sodium pump 期刊论文
NATURE, 2020, 583 (7815) : 314-+
作者:  Moore, Luiza;  Leongamornlert, Daniel;  Coorens, Tim H. H.;  Sanders, Mathijs A.;  Ellis, Peter;  Dentro, Stefan C.;  Dawson, Kevin J.;  Butler, Tim;  Rahbari, Raheleh;  Mitchell, Thomas J.;  Maura, Francesco;  Nangalia, Jyoti;  Tarpey, Patrick S.;  Brunner, Simon F.;  Lee-Six, Henry;  Hooks, Yvette;  Moody, Sarah;  Mahbubani, Krishnaa T.;  Jimenez-Linan, Mercedes;  Brosens, Jan J.;  Iacobuzio-Donahue, Christine A.;  Martincorena, Inigo;  Saeb-Parsy, Kourosh;  Campbell, Peter J.;  Stratton, Michael R.
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

Light-driven sodium pumps actively transport small cations across cellular membranes(1). These pumps are used by microorganisms to convert light into membrane potential and have become useful optogenetic tools with applications in neuroscience. Although the resting state structures of the prototypical sodium pump Krokinobacter eikastus rhodopsin 2 (KR2) have been solved(2,3), it is unclear how structural alterations overtime allow sodium to be translocated against a concentration gradient. Here, using the Swiss X-ray Free Electron Laser(4), we have collected serial crystallographic data at ten pump-probe delays from femtoseconds to milliseconds. High-resolution structural snapshots throughout the KR2 photocycle show how retinal isomerization is completed on the femtosecond timescale and changes the local structure of the binding pocket in the early nanoseconds. Subsequent rearrangements and deprotonation of the retinal Schiff base open an electrostatic gate in microseconds. Structural and spectroscopic data, in combination with quantum chemical calculations, indicate that a sodium ion bind stransiently close to the retinal within one millisecond. In the last structural intermediate, at 20 milliseconds after activation, we identified a potential second sodium-binding site close to the extracellular exit. These results provide direct molecular insight into the dynamics of active cation transport across biological membranes.


  
Mapping the twist-angle disorder and Landau levels in magic-angle graphene 期刊论文
NATURE, 2020, 581 (7806) : 47-+
作者:  Luck, Katja;  39;Amata, Cassandra
收藏  |  浏览/下载:11/0  |  提交时间:2020/07/03

The recently discovered flat electronic bands and strongly correlated and superconducting phases in magic-angle twisted bilayer graphene (MATBG)(1,2) crucially depend on the interlayer twist angle, theta. Although control of the global theta with a precision of about 0.1 degrees has been demonstrated(1-7), little information is available on the distribution of the local twist angles. Here we use a nanoscale on-tip scanning superconducting quantum interference device (SQUID-on-tip)(8) to obtain tomographic images of the Landau levels in the quantum Hall state(9) and to map the local theta variations in hexagonal boron nitride (hBN)-encapsulated MATBG devices with relative precision better than 0.002 degrees and a spatial resolution of a few moire periods. We find a correlation between the degree of theta disorder and the quality of the MATBG transport characteristics and show that even state-of-the-art devices-which exhibit correlated states, Landau fans and superconductivity-display considerable local variation in theta of up to 0.1 degrees, exhibiting substantial gradients and networks of jumps, and may contain areas with no local MATBG behaviour. We observe that the correlated states in MATBG are particularly fragile with respect to the twist-angle disorder. We also show that the gradients of theta generate large gate-tunable in-plane electric fields, unscreened even in the metallic regions, which profoundly alter the quantum Hall state by forming edge channels in the bulk of the sample and may affect the phase diagram of the correlated and superconducting states. We thus establish the importance of theta disorder as an unconventional type of disorder enabling the use of twist-angle gradients for bandstructure engineering, for realization of correlated phenomena and for gate-tunable built-in planar electric fields for device applications.


SQUID-on-tip tomographic imaging of Landau levels in magic-angle graphene provides nanoscale maps of local twist-angle disorder and shows that its properties are fundamentally different from common types of disorder.


  
LEM2 phase separation promotes ESCRT-mediated nuclear envelope reformation 期刊论文
NATURE, 2020
作者:  Deshaies, Raymond J.
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/03

Following cell division, phase separation of the transmembrane adaptor LEM2 ensures that the ESCRT machinery remodels microtubules and seals the nuclear envelope.


During cell division, remodelling of the nuclear envelope enables chromosome segregation by the mitotic spindle(1). The reformation of sealed nuclei requires ESCRTs (endosomal sorting complexes required for transport) and LEM2, a transmembrane ESCRT adaptor(2-4). Here we show how the ability of LEM2 to condense on microtubules governs the activation of ESCRTs and coordinated spindle disassembly. The LEM motif of LEM2 binds BAF, conferring on LEM2 an affinity for chromatin(5,6), while an adjacent low-complexity domain (LCD) promotes LEM2 phase separation. A proline-arginine-rich sequence within the LCD binds to microtubules and targets condensation of LEM2 to spindle microtubules that traverse the nascent nuclear envelope. Furthermore, the winged-helix domain of LEM2 activates the ESCRT-II/ESCRT-III hybrid protein CHMP7 to form co-oligomeric rings. Disruption of these events in human cells prevented the recruitment of downstream ESCRTs, compromised spindle disassembly, and led to defects in nuclear integrity and DNA damage. We propose that during nuclear reassembly LEM2 condenses into a liquid-like phase and coassembles with CHMP7 to form a macromolecular O-ring seal at the confluence between membranes, chromatin and the spindle. The properties of LEM2 described here, and the homologous architectures of related inner nuclear membrane proteins(7,8), suggest that phase separation may contribute to other critical envelope functions, including interphase repair(8-13) and chromatin organization(14-17).


  
Liquid flow and control without solid walls 期刊论文
NATURE, 2020, 581 (7806) : 58-+
作者:  Hellmuth, Susanne;  Stemmann, Olaf
收藏  |  浏览/下载:40/0  |  提交时间:2020/07/03

Wall-free liquid channels surrounded by an immiscible magnetic liquid can be used to create liquid circuitry or to transport human blood without damaging the blood cells by moving permanent magnets.


When miniaturizing fluidic circuitry, the solid walls of the fluid channels become increasingly important(1) because they limit the flow rates achievable for a given pressure drop, and they are prone to fouling(2). Approaches for reducing the wall interactions include hydrophobic coatings(3), liquid-infused porous surfaces(4-6), nanoparticle surfactant jamming(7), changes to surface electronic structure(8), electrowetting(9,10), surface tension pinning(11,12) and use of atomically flat channels(13). A better solution may be to avoid the solid walls altogether. Droplet microfluidics and sheath flow achieve this but require continuous flow of the central liquid and the surrounding liquid(1,14). Here we demonstrate an approach in which aqueous liquid channels are surrounded by an immiscible magnetic liquid, both of which are stabilized by a quadrupolar magnetic field. This creates self-healing, non-clogging, anti-fouling and near-frictionless liquid-in-liquid fluidic channels. Manipulation of the field provides flow control, such as valving, splitting, merging and pumping. The latter is achieved by moving permanent magnets that have no physical contact with the liquid channel. We show that this magnetostaltic pumping method can be used to transport whole human blood with very little damage due to shear forces. Haemolysis (rupture of blood cells) is reduced by an order of magnitude compared with traditional peristaltic pumping, in which blood is mechanically squeezed through a plastic tube. Our liquid-in-liquid approach provides new ways to transport delicate liquids, particularly when scaling channels down to the micrometre scale, with no need for high pressures, and could also be used for microfluidic circuitry.