RESUMO
OSCA/TMEM63 channels are the largest known family of mechanosensitive channels1-3, playing critical roles in plant4-7 and mammalian8,9 mechanotransduction. Here we determined 44 cryogenic electron microscopy structures of OSCA/TMEM63 channels in different environments to investigate the molecular basis of OSCA/TMEM63 channel mechanosensitivity. In nanodiscs, we mimicked increased membrane tension and observed a dilated pore with membrane access in one of the OSCA1.2 subunits. In liposomes, we captured the fully open structure of OSCA1.2 in the inside-in orientation, in which the pore shows a large lateral opening to the membrane. Unusually for ion channels, structural, functional and computational evidence supports the existence of a 'proteo-lipidic pore' in which lipids act as a wall of the ion permeation pathway. In the less tension-sensitive homologue OSCA3.1, we identified an 'interlocking' lipid tightly bound in the central cleft, keeping the channel closed. Mutation of the lipid-coordinating residues induced OSCA3.1 activation, revealing a conserved open conformation of OSCA channels. Our structures provide a global picture of the OSCA channel gating cycle, uncover the importance of bound lipids and show that each subunit can open independently. This expands both our understanding of channel-mediated mechanotransduction and channel pore formation, with important mechanistic implications for the TMEM16 and TMC protein families.
Assuntos
Canais de Cálcio , Microscopia Crioeletrônica , Ativação do Canal Iônico , Mecanotransdução Celular , Humanos , Anoctaminas/química , Anoctaminas/metabolismo , Canais de Cálcio/química , Canais de Cálcio/metabolismo , Canais de Cálcio/ultraestrutura , Lipídeos/química , Lipossomos/metabolismo , Lipossomos/química , Modelos Moleculares , Nanoestruturas/químicaRESUMO
Cristae membrane state plays a central role in regulating mitochondrial function and cellular metabolism. The protein Optic atrophy 1 (Opa1) is an important crista remodeler that exists as two forms in the mitochondrion, a membrane-anchored long form (l-Opa1) and a processed short form (s-Opa1). The mechanisms for how Opa1 influences cristae shape have remained unclear due to lack of native three-dimensional views of cristae. We perform in situ cryo-electron tomography of cryo-focused ion beam milled mouse embryonic fibroblasts with defined Opa1 states to understand how each form of Opa1 influences cristae architecture. In our tomograms, we observe a variety of cristae shapes with distinct trends dependent on s-Opa1:l-Opa1 balance. Increased l-Opa1 levels promote cristae stacking and elongated mitochondria, while increased s-Opa1 levels correlated with irregular cristae packing and round mitochondria shape. Functional assays indicate a role for l-Opa1 in wild-type apoptotic and calcium handling responses, and show a compromised respiratory function under Opa1 imbalance. In summary, we provide three-dimensional visualization of cristae architecture to reveal relationships between mitochondrial ultrastructure and cellular function dependent on Opa1-mediated membrane remodeling.
Assuntos
Fibroblastos , Membranas Mitocondriais , Animais , Camundongos , Fibroblastos/metabolismo , Membranas Mitocondriais/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismoRESUMO
We present reciprocal polarization imaging for the optical activity of chiral media in reflection geometry. The method is based on the reciprocal polar decomposition of backscattering Mueller matrices accounting for the reciprocity of light waves in forward and backward scattering paths. Anisotropic depolarization is introduced to gain sensitivity to optical activity in backscattering. Experiments with glucose solutions show that while the Lu-Chipman decomposition of the backscattering Mueller matrices produces erroneous results, reciprocal polarization imaging correctly retrieves the optical activity of chiral media. The recovered optical rotation agrees with that obtained in the forward geometry and increases linearly with the concentration and thickness of the chiral media. The potential for in vivo glucose monitoring based on optical activity sensing using reciprocal polarization imaging is then discussed.
RESUMO
Magnetic responsive ionic liquid (MIL) demonstrated an advanced photomobility in confined narrow spaces through the doping of photoresponsive azobenzene by the interplay of supramolecular π-cations. Moreover, reversible physisorption/desorption of CO2 was achieved based on the photocontrolled solid-liquid transitions of the mixtures. Our approach opens opportunities to obtain multi-stimuli response through the coordinated supramolecular interplay of each responsive component.
RESUMO
The thermal runaway issue represents a long-standing obstacle that retards large-scale applications of lithium metal batteries. Various approaches to inhibit thermal runaway suffer from some intrinsic drawbacks, either being irreversible or delayed thermal protection. Herein, this work has explored thermo-responsive lower critical solution temperature (LCST) ionic liquid-based electrolytes, which provides reversible overheating protection for batteries with warning and shut-down stages, well corresponding to an initial stage of thermal runaway process. The batteries could function stably below 70 °C as a working mode, while demonstrating a warning mode above 80 °C with a noticeable reduction in specific capacitance to delay temperature increase of batteries. In terms of 110 °C as a critically dangerous temperature, a shut-down mode is designed to minimize the thermal energy releasing as the batteries are barely chargeable and dischargeable. Dynamically growing polymeric particles above LCST contributed to such an intelligent and mild control on specific capacitance. Larger size will occupy larger surfaces of electrodes and close more pores of separators, enabling a gradual suppressing of Li+ transfer and reactions. The present work demonstrated a scientific design of thermoresponsive LCST electrolytes with a superiorly precise and intelligent control of electrochemical performances to achieve self-adapted overheating protections.
RESUMO
Nuclear speckles (NSs) are nuclear biomolecular condensates that are postulated to form by macromolecular phase separation, although the detailed underlying forces driving NS formation remain elusive. SRRM2 and SON are 2 non-redundant scaffold proteins for NSs. How each individual protein governs assembly of the NS protein network and the functional relationship between SRRM2 and SON are largely unknown. Here, we uncover immiscible multiphases of SRRM2 and SON within NSs. SRRM2 and SON are functionally independent, specifically regulating alternative splicing of subsets of mRNA targets, respectively. We further show that SRRM2 forms multicomponent liquid phases in cells to drive NS subcompartmentalization, which is reliant on homotypic interaction and heterotypic non-selective protein-RNA complex coacervation-driven phase separation. SRRM2 serine/arginine-rich (RS) domains form higher-order oligomers and can be replaced by oligomerizable synthetic modules. The serine residues within the RS domains, however, play an irreplaceable role in fine-tuning the liquidity of NSs.
Assuntos
Salpicos Nucleares , Proteínas de Ligação a RNA , Proteínas de Ligação a RNA/metabolismo , Separação de Fases , Processamento Alternativo/genética , Serina/metabolismoRESUMO
Smart windows always respond to single stimuli, which cannot satisfy various needs in practical applications. Smart windows that integrate thermotropic, electrochromic and power-generating functions in one device is highly challenging yet important in satisfying on-demand light modulation and energy efficiency in practical applications. Herein, a thermoresponsive lower critical solution temperature (LCST) ion gel was fabricated via a facile in situ polymerization of butyl acrylate in a conventional ionic liquid to explore "all in one" smart windows. The ion gel-assembled smart windows are thermotropic and electrochromic with a reliable adjustment of light transparency as well as power-generating, enabled by the ionic Soret effect of ionic liquids. Additionally, the ion gels demonstrated self-defensive robust mechanical properties, thermal insulating and antifogging properties. With such an interdisciplinary and comprehensive study of the ion gels, the LCST ion gels could fulfil the requirements of genius windows with high energy-saving potential and exceptional climate adaptability, such as shut-down of light transmission in summer, daily solar energy collection, and colour changes on demand. It conceptually updates smart windows from an energy saving to an energy supplier in buildings. It is the first time to explore the "all in one" smart windows based on integrated multifunctional ionic liquids, which could greatly bridge the gap between the materials and buildings to accelerate practical applications of smart windows.