Transient receptor potential canonical (TRPC) channels TRPC3, TRPC6 and TRPC7 are able to sense the lipid messenger diacylglycerol (DAG). The DAG-sensing and lipid-gating processes in these ion channels are still unknown. To gain insights into the lipid-sensing principle, we generated a DAG photoswitch, OptoDArG, that enabled efficient control of TRPC3 by light. A structure-guided mutagenesis screen of the TRPC3 pore domain unveiled a single glycine residue behind the selectivity filter (G652) that is exposed to lipid through a subunit-joining fenestration. Exchange of G652 with larger residues altered the ability of TRPC3 to discriminate between different DAG molecules. Light-controlled activation-deactivation cycling of TRPC3 channels by an OptoDArG-mediated optical 'lipid clamp' identified pore domain fenestrations as pivotal elements of the channel´s lipid-sensing machinery. We provide evidence for a novel concept of lipid sensing by TRPC channels based on a lateral fenestration in the pore domain that accommodates lipid mediators to control gating.
Type VI Secretion Systems (T6SS), widely distributed in Gram-negative bacteria, contribute to interbacterial competition and pathogenesis through the translocation of effector proteins to target cells. harbor 5 pathogenicity islands encoding T6SS (SPI-6, SPI-19, SPI-20, SPI-21 and SPI-22), in which a limited number of effector proteins have been identified. Previous analyses by our group focused on the identification of candidate T6SS effectors and cognate immunity proteins in genomes deposited in public databases.
Two-pore domain, outwardly rectifying potassium (TOK) channels are exclusively expressed in fungi. Human fungal pathogen TOK channels are potential antifungal targets, but TOK channel modulation in general is poorly understood. Here, we discovered that TOK (CaTOK) is regulated by extracellular pH, in contrast to TOK channels from other fungal species tested.
Cellular and Molecular Physiology, School of Medicine, Yale University, New Haven, CT; Nanobiology Institute, Yale University, West Haven, CT; Molecular Biophysics and Biochemistry, Yale University, New Haven, CT; Saints-Pères Paris Institute for the Neurosciences (SPPIN), Université de Paris, Centre National de la Recherche Scientifique (CNRS) UMR 8003, Paris, France; Wu Tsai Institute, Yale University. Electronic address:
Synaptotagmin-1 (Syt1) is a major calcium sensor for rapid neurotransmitter release in neurons and hormone release in many neuroendocrine cells. It possesses two tandem cytosolic C2 domains that bind calcium, negatively charged phospholipids, and the neuronal SNARE complex. Calcium binding to Syt1 triggers exocytosis, but how this occurs is not well understood.
State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, Beijing Frontier Research Center of Biological Structure, Tsinghua University, Beijing 100084, China; School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China; IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing 100084, China. Electronic address:
PIEZO1 is a mechanically activated cation channel that undergoes force-induced activation and inactivation. However, its distinct structural states remain undefined. Here, we employed an open-prone PIEZO1-S2472E mutant to capture an intermediate open structure.
Advanced porous nanomaterials have recently been the subject of considerable interest due to their high surface areas, tunable pore structures, high porosity, and ease of modification. In the chemiluminescence (CL) domain, the incorporation of additional pores into nanostructures not only enhances the loading capacity for signal amplification but also allows the confinement effect in a nanoscale microreactor and the controlled release of reaction agents. In light of this, increasing efforts have been made to fabricate various porous nanomaterials and explore their potential applications in CL assays.
