Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn²⁺ uptake into the Golgi apparatus

クライオ電子顕微鏡により、ゴルジ体の亜鉛輸送体による亜鉛輸送機構の全容を解明 細胞の亜鉛恒常性維持機構の理解に大きな進展. 京都大学プレスリリース. 2023-08-29.Zinc ions (Zn²⁺) are vital to most cells, with the intracellular concentrations of Zn²⁺ being tightly regulated by multiple zinc transporters located at the plasma and organelle membranes. We herein present the 2.2-3.1 Å-resolution cryo-EM structures of a Golgi-localized human Zn²⁺/H+ antiporter ZnT7 (hZnT7) in Zn²⁺-bound and unbound forms. Cryo-EM analyses show that hZnT7 exists as a dimer via tight interactions in both the cytosolic and transmembrane (TM) domains of two protomers, each of which contains a single Zn²⁺-binding site in its TM domain. hZnT7 undergoes a TM-helix rearrangement to create a negatively charged cytosolic cavity for Zn²⁺ entry in the inward-facing conformation and widens the luminal cavity for Zn²⁺ release in the outward-facing conformation. An exceptionally long cytosolic histidine-rich loop characteristic of hZnT7 binds two Zn²⁺ ions, seemingly facilitating Zn²⁺ recruitment to the TM metal transport pathway. These structures permit mechanisms of hZnT7-mediated Zn²⁺ uptake into the Golgi to be proposed

STING signalling is terminated through ESCRT-dependent microautophagy of vesicles originating from recycling endosomes

STING炎症シグナルの終結分子機構 --新規細胞内分解システムの発見--. 京都大学プレスリリース. 2023-03-14.Stimulator of interferon genes (STING) is essential for the type I interferon response against a variety of DNA pathogens. Upon emergence of cytosolic DNA, STING translocates from the endoplasmic reticulum to the Golgi where STING activates the downstream kinase TBK1, then to lysosome through recycling endosomes (REs) for its degradation. Although the molecular machinery of STING activation is extensively studied and defined, the one underlying STING degradation and inactivation has not yet been fully elucidated. Here we show that STING is degraded by the endosomal sorting complexes required for transport (ESCRT)-driven microautophagy. Airyscan super-resolution microscopy and correlative light/electron microscopy suggest that STING-positive vesicles of an RE origin are directly encapsulated into Lamp1-positive compartments. Screening of mammalian Vps genes, the yeast homologues of which regulate Golgi-to-vacuole transport, shows that ESCRT proteins are essential for the STING encapsulation into Lamp1-positive compartments. Knockdown of Tsg101 and Vps4, components of ESCRT, results in the accumulation of STING vesicles in the cytosol, leading to the sustained type I interferon response. Knockdown of Tsg101 in human primary T cells leads to an increase the expression of interferon-stimulated genes. STING undergoes K63-linked ubiquitination at lysine 288 during its transit through the Golgi/REs, and this ubiquitination is required for STING degradation. Our results reveal a molecular mechanism that prevents hyperactivation of innate immune signalling, which operates at REs

Syntheses, crystal structures and adsorption properties of ultramicroporous coordination polymers constructed from hexafluorosilicate ions and pyrazine

The cover picture The cover picture shows two crystal structures of porous coordination polymers, [Cu(SiF<SUB>6</SUB>)(4,4′bpy)<SUB>2</SUB>]<SUB>n</SUB> and [Zn(SiF<SUB>6</SUB>)(pyz)<SUB>2</SUB>]<SUB>n</SUB> (4,4′‐bpy = 4,4′‐bipyridine, pyz = pyrazine), which have been generated from square‐grid coordination polymers that are cross‐linked by ν‐SiF<SUB>6</SUB> anions. Although typical bridging ligands such as 4,4′‐bpy and 1,4‐benzenedicarboxylate produce open octahedral coordination polymers with micropores, such micropores need to be further narrowed to become ultramicropores (&#x0003C; 7 &#x000C5;) for separation and purification of smaller gas molecules. We have succeeded in obtaining the ultramicroporous coordination polymer [Zn(SiF<SUB>6</SUB>)(pyz) <SUB>2</SUB>]<SUB>n</SUB> with 4.5 &#x000B1; 4.5 &#x000C5;<SUP>2</SUP> pores by simply replacing 4,4′‐bpy in [M(SiF<SUB>6</SUB>)(4,4′‐bpy)<SUB>2</SUB>] <SUB>n</SUB> (M = Zn<SUP>2+</SUP>, Cu<SUP>2+</SUP>) with pyz. The ultramicropores of [Zn(SiF<SUB>6</SUB>)(pyz)<SUB>2</SUB>]<SUB>n</SUB> adsorb Me<SUB>2</SUB>CO rather than iPrOH, showing the size‐exclusive effect. Additionally this compound shows a sharp uptake in H<SUB>2</SUB> adsorption at 77 K, because the interaction potential is expected to be strong as a result of the synergistic effect of the neighbouring pore walls. Details are discussed in the article by K. Uemura et al. on p. 2329 ff

Microstructure Investigation of Polymer Electrolyte Fuel Cell Catalyst Layers Containing Perfluorosulfonated Ionomer

Perfluorosulfonated ionomers are the most successful ion-exchange membranes at an industrial scale. One recent, cutting-edge application of perfluorosulfonated ionomers is in polymer electrolyte fuel cells (PEFCs). In PEFCs, the ionomers are used as a component of the catalyst layer (CL) in addition to functioning as a proton-exchange membrane. In this study, the microstructures in the CLs of PEFCs were characterized by combined synchrotron X-ray scattering and transmission electron microscopy (TEM) analyses. The CL comprised a catalyst, a support, and an ionomer. Fractal dimensional analysis of the combined ultrasmall- and small-angle X-ray scattering profiles indicated that the carbon-black-supported Pt catalyst (Pt/CB) surface was covered with the ionomer in the CL. Anomalous X-ray scattering revealed that the Pt catalyst nanoparticles on the carbon surfaces were aggregated in the CLs. These findings are consistent with the ionomer/catalyst microstructures and ionomer coverage on the Pt/CB surface obtained from TEM observations