A5088481317- Photosynthetic Processes and Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Microbial Metabolites in Food Biotechnology
- Glycosylation and Glycoproteins Research
- Mesoporous Materials and Catalysis
- Cellular transport and secretion
- Autophagy in Disease and Therapy
- Toxin Mechanisms and Immunotoxins
- Metalloenzymes and iron-sulfur proteins
- ATP Synthase and ATPases Research
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Enzyme Structure and Function
- Fluorine in Organic Chemistry
- Animal Virus Infections Studies
- Peptidase Inhibition and Analysis
- SARS-CoV-2 and COVID-19 Research
- Metabolomics and Mass Spectrometry Studies
- RNA modifications and cancer
- RNA Interference and Gene Delivery
- Bacteriophages and microbial interactions
University of California, Berkeley
2018-2024
Gilead Sciences (United States)
2024
Quantitative BioSciences
2022
QB3
2022
University of California, Los Angeles
2018
Berkeley College
2018
Posttranslational translocon architecture About a third of proteins are transported into endoplasmic reticulum by the universally conserved Sec61 protein-conducting channel. Itskanov and Park determined cryo–electron microscopy structure Sec complex from yeast, which mediates posttranslational translocation many secretory across membrane. The study reveals how Sec63 activates channel for substrate polypeptide insertion. also explains mutually exclusive binding ribosome to Science , this issue p. 84
Coronavirus replication is understood to occur within double membrane vesicles (DMVs) that arise during viral infection. Prior work has determined these DMVs have characteristic pores formed from the non-structural proteins nsp3 and nsp4, which facilitate export of newly synthesized RNA. Yet how machinery, minimally comprised nsp7 nsp16, recruited DMV remains a mystery. Working AlphaFold previously structures, we constructed series models link formation pore nsp5 protease processing...
Abstract Doa10 (MARCHF6 in metazoans) is a large polytopic membrane-embedded E3 ubiquitin ligase the endoplasmic reticulum (ER) that plays an important role quality control of cytosolic and ER proteins. Although highly conserved across eukaryotes, it not understood how recognizes its substrates. Here, we define substrate recognition mechanism by structural functional analyses on Saccharomyces cerevisiae model Cryo-EM analysis shows has unusual architecture with lipid-filled central cavity,...
Abstract Mitochondria are cellular organelles with crucial functions in the generation and distribution of ATP, buffering cytosolic Ca 2+ initiation apoptosis. Compounds that interfere these termed mitochondrial toxins, many which derived from microbes, such as antimycin A, oligomycin ionomycin. Here, we identify mycotoxin phomoxanthone A (PXA), endophytic fungus Phomopsis longicolla , a toxin. We show PXA elicits strong release mitochondria but not ER. In addition, depolarises similarly to...
Abstract The Sec61 complex forms a protein-conducting channel in the endoplasmic reticulum (ER) membrane that is required for secretion of soluble proteins and production many proteins. Several natural synthetic small molecules specifically inhibit channel, generating cellular effects are potentially useful therapeutic purposes, but their inhibitory mechanisms remain unclear. Here we present near-atomic-resolution structures human inhibited by comprehensive panel structurally distinct...
Doa10 (MARCH6 in metazoans) is a large polytopic membrane-embedded E3 ubiquitin ligase the endoplasmic reticulum (ER) that plays an important role quality control of cytosolic and ER proteins. Although highly conserved across eukaryotes, it not understood how recognizes its substrates. Here, we defined substrate recognition mechanism by structural functional analyses on Saccharomyces cerevisiae well-defined degron Deg1. Cryo-EM analysis shows has unusual architecture with lipid-filled...
Mfn2 is a mitochondrial outer membrane fusion protein with the additional role of tethering mitochondria to ER. Here, we describe novel connection between and calcium release from mitochondria. We show that controls inner sodium-calcium exchange NCLX, which major source for This discovery was made fungal toxin Phomoxanthone (PXA), induces PXA-induced blocked by chemical inhibitor while NCLX deletions both also prevent release. CETSA experiments PXA directly targets Mfn2, likely through...
Abstract Autophagy involves rapid growth of phagophores through membrane addition. Newly added membranes are derived from other organelles vesicles carrying the Atg9 protein. Membrane is delivered by fusing these with phagophores. is, nevertheless, not incorporated in autophagosomes. We now show that this protein retrieved fission utilizing Dynamin-2 (Dnm2) as scission Blocking recycling interfering Dnm2 helps retain autophagosomes and degrades autophagy. colocalizes BAR domain Endophilin-B1...
Summary The universally conserved Sec61/SecY channel mediates transport of many newly synthesized polypeptides across membranes, an essential step in protein secretion and membrane integration 1-5 . has two gating mechanisms—a lipid-facing lateral gate, through which hydrophobic signal sequences or transmembrane helices (TMs) are released into the membrane, a vertical called plug, regulates water-filled pore required for translocation hydrophilic polypeptide segments 6 Currently, how these...