The mitochondrial DNAJC co-chaperone TCAIM reduces α-ketoglutarate dehydrogenase protein levels to regulate metabolism.

Mitochondrial heat shock proteins and co-chaperones play crucial roles in maintaining proteostasis by regulating unfolded proteins, usually without specific target preferences. In this study, we identify a DNAJC-type co-chaperone: T cell activation inhibitor, mitochondria (TCAIM), and demonstrate its specific binding to α-ketoglutarate dehydrogenase (OGDH), a key rate-limiting enzyme in mitochondrial metabolism. This interaction suppresses OGDH function and subsequently reduces carbohydrate catabolism in both cultured cells and murine models.

Structure of a unique PSII-Pcb tetrameric megacomplex in a chlorophyll -containing cyanobacterium.

is a unique cyanobacterium using chlorophyll (Chl ) as its major pigment and thus can use far-red light for photosynthesis. Photosystem II (PSII) of associates with a number of prochlorophyte Chl-binding (Pcb) proteins to act as the light-harvesting system. We report here the cryo-electron microscopic structure of a PSII-Pcb megacomplex from at a 3.

Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants.

The constant emergence of SARS-CoV-2 variants continues to impair the efficacy of existing neutralizing antibodies, especially XBB.1.5 and EG.

Pangenome analysis reveals genomic variations associated with domestication traits in broomcorn millet.

Broomcorn millet (Panicum miliaceum L.) is an orphan crop with the potential to improve cereal production and quality, and ensure food security. Here we present the genetic variations, population structure and diversity of a diverse worldwide collection of 516 broomcorn millet genomes.

Architecture of the baculovirus nucleocapsid revealed by cryo-EM.

Baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) has been widely used as a bioinsecticide and a protein expression vector. Despite their importance, very little is known about the structure of most baculovirus proteins. Here, we show a 3.

STT3A-mediated viral N-glycosylation underlies the tumor selectivity of oncolytic virus M1.

Oncolytic viruses are emerging as promising anticancer agents. Although the essential biological function of N-glycosylation on viruses are widely accepted, roles of N-glycan and glycan-processing enzyme in oncolytic viral therapy are remain elusive. Here, via cryo-EM analysis, we identified three distinct N-glycans on the envelope of oncolytic virus M1 (OVM) as being necessary for efficient receptor binding.

Directed natural evolution generates a next-generation oncolytic virus with a high potency and safety profile.

Oncolytic viruses (OVs) represent a type of encouraging multi-mechanistic drug for the treatment of cancer. However, attenuation of virulence, which is generally required for the development of OVs based on pathogenic viral backbones, is frequently accompanied by a compromised killing effect on tumor cells. By exploiting the property of viruses to evolve and adapt in cancer cells, we perform directed natural evolution on refractory colorectal cancer cell HCT-116 and generate a next-generation oncolytic virus M1 (NGOVM) with an increase in the oncolytic effect of up to 9690-fold.

Cryo-EM structures of ClC-2 chloride channel reveal the blocking mechanism of its specific inhibitor AK-42.

ClC-2 transports chloride ions across plasma membranes and plays critical roles in cellular homeostasis. Its dysfunction is involved in diseases including leukodystrophy and primary aldosteronism. AK-42 was recently reported as a specific inhibitor of ClC-2.

A straight-forward seed production technology system for foxtail millet (Setaria italica).

For autogamous crops, a precondition for using heterosis is to produce sufficient pure male-sterile female parents that can be used to produce hybrid seeds. To date, cytoplasmic male sterility (CMS) and environment-sensitive genic male sterility (EGMS) have been used commercially to exploit heterosis for autogamous species. However, neither CMS nor EGMS has been established for foxtail millet (Setaria italica).

The structure of a 12-segmented dsRNA reovirus: New insights into capsid stabilization and organization.

Infecting a wide range of hosts, members of Reovirales (formerly Reoviridae) consist of a genome with different numbers of segmented double stranded RNAs (dsRNA) encapsulated by a proteinaceous shell and carry out genome replication and transcription inside the virion. Several cryo-electron microscopy (cryo-EM) structures of reoviruses with 9, 10 or 11 segmented dsRNA genomes have revealed insights into genome arrangement and transcription. However, the structure and genome arrangement of 12-segmented Reovirales members remain poorly understood.

Applications and prospects of cryo-EM in drug discovery.

Drug discovery is a crucial part of human healthcare and has dramatically benefited human lifespan and life quality in recent centuries, however, it is usually time- and effort-consuming. Structural biology has been demonstrated as a powerful tool to accelerate drug development. Among different techniques, cryo-electron microscopy (cryo-EM) is emerging as the mainstream of structure determination of biomacromolecules in the past decade and has received increasing attention from the pharmaceutical industry.

Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5.

SARS-CoV-2 Omicron subvariants have demonstrated extensive evasion from monoclonal antibodies (mAbs) developed for clinical use, which raises an urgent need to develop new broad-spectrum mAbs. Here, we report the isolation and analysis of two anti-RBD neutralizing antibodies BA7208 and BA7125 from mice engineered to produce human antibodies. While BA7125 showed broadly neutralizing activity against all variants except the Omicron sublineages, BA7208 was potently neutralizing against all tested SARS-CoV-2 variants (including Omicron BA.

Cryo-EM Structure and Activator Screening of Human Tryptophan Hydroxylase 2.

Human tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in the synthesis of serotonin. Its dysfunction has been implicated in various psychiatric disorders such as depression, autism, and bipolar disorder. TPH2 is typically decreased in stability and catalytic activity in patients; thus, screening of molecules capable of binding and stabilizing the structure of TPH2 in activated conformation is desired for drug development in mental disorder treatment.

Omicron SARS-CoV-2 mutations stabilize spike up-RBD conformation and lead to a non-RBM-binding monoclonal antibody escape.

Omicron SARS-CoV-2 is rapidly spreading worldwide. To delineate the impact of emerging mutations on spike's properties, we performed systematic structural analyses on apo Omicron spike and its complexes with human ACE2 or S309 neutralizing antibody (NAb) by cryo-EM. The Omicron spike preferentially adopts the one-RBD-up conformation both before and after ACE2 binding, which is in sharp contrast to the orchestrated conformational changes to create more up-RBDs upon ACE2 binding as observed in the prototype and other four variants of concern (VOCs).

The phosphorylation and dephosphorylation switch of VCP/p97 regulates the architecture of centrosome and spindle.

The proper orientation of centrosome and spindle is essential for genome stability; however, the mechanism that governs these processes remains elusive. Here, we demonstrated that polo-like kinase 1 (Plk1), a key mitotic kinase, phosphorylates residue Thr76 in VCP/p97 (an AAA-ATPase), at the centrosome from prophase to anaphase. This phosphorylation process recruits VCP to the centrosome and in this way, it regulates centrosome orientation.

Structural basis for the activity and regulation of human α-ketoglutarate dehydrogenase revealed by Cryo-EM.

The human mitochondrial alpha-ketoglutarate (α-KG) dehydrogenase complex (hKGDHc) is a well-studied macromolecular enzyme that converts α-KG to succinyl-CoA and NADH. Abnormalities of the complex lead to several diseases, including neurodegenerative disorders. Despite its importance in human metabolism and diseases, structural information on hKGDHc is not well defined.

Structure of infective Getah virus at 2.8 Å resolution determined by cryo-electron microscopy.

Getah virus (GETV), a member of the genus alphavirus, is a mosquito-borne pathogen that can cause pyrexia and reproductive losses in animals. Although antibodies to GETV have been found in over 10% of healthy people, there are no reports of clinical symptoms associated with GETV. The biological and pathological properties of GETV are largely unknown and antiviral or vaccine treatments against GETV are still unavailable due to a lack of knowledge of the structure of the GETV virion.

Cryo-electron Tomography Reveals the Roles of FliY in Flagellar Motor Assembly.

Helicobacter pylori plays a causative role in gastric diseases. The pathogenicity of H. pylori depends on its ability to colonize the stomach guided by motility.

Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic continues worldwide with many variants arising, some of which are variants of concern (VOCs). A recent VOC, omicron (B.1.

The role of AUX1 during lateral root development in the domestication of the model C4 grass Setaria italica.

C4 photosynthesis increases the efficiency of carbon fixation by spatially separating high concentrations of molecular oxygen from Rubisco. The specialized leaf anatomy required for this separation evolved independently many times. The morphology of C4 root systems is also distinctive and adapted to support high rates of photosynthesis; however, little is known about the molecular mechanisms that have driven the evolution of C4 root system architecture.

Cryo-EM reveals a previously unrecognized structural protein of a dsRNA virus implicated in its extracellular transmission.

Mosquito viruses cause unpredictable outbreaks of disease. Recently, several unassigned viruses isolated from mosquitoes, including the Omono River virus (OmRV), were identified as totivirus-like viruses, with features similar to those of the Totiviridae family. Most reported members of this family infect fungi or protozoans and lack an extracellular life cycle stage.

The Architecture of Inactivated SARS-CoV-2 with Postfusion Spikes Revealed by Cryo-EM and Cryo-ET.

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) resulted from the outbreak of SARS-CoV-2 in December 2019. Currently, multiple efforts are being made to rapidly develop vaccines and treatments to fight COVID-19. Current vaccine candidates use inactivated SARS-CoV-2 viruses; therefore, it is important to understand the architecture of inactivated SARS-CoV-2.