A5074800971- Viral Infections and Vectors
- Bacteriophages and microbial interactions
- Viral Infections and Outbreaks Research
- RNA and protein synthesis mechanisms
- Mosquito-borne diseases and control
- Viral gastroenteritis research and epidemiology
- Viral Infections and Immunology Research
- Genomics and Phylogenetic Studies
- Virus-based gene therapy research
- Vector-Borne Animal Diseases
- Plant Virus Research Studies
- Fire effects on ecosystems
- Enzyme Structure and Function
- Respiratory viral infections research
- Advanced Electron Microscopy Techniques and Applications
- RNA modifications and cancer
- Endoplasmic Reticulum Stress and Disease
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- Photoreceptor and optogenetics research
- Viral Infectious Diseases and Gene Expression in Insects
- RNA regulation and disease
- Lipid Membrane Structure and Behavior
- Cytomegalovirus and herpesvirus research
- Nonlinear Optical Materials Research
University of Helsinki
2011-2025
California State University Los Angeles
2024
University of Florida
2024
Czech Academy of Sciences, Institute of Biotechnology
2023
University of Oxford
2012-2021
Centre for Human Genetics
2012-2021
Hospital District of Helsinki and Uusimaa
2021
Helsinki University Hospital
2021
University of Zurich
2021
Biocenter Finland
2005-2021
Electron cryomicroscopy can yield near-atomic resolution structures of highly ordered macromolecular complexes. Often however some subunits bind in a flexible manner, have different symmetry from the rest complex, or are present sub-stoichiometric amounts, limiting attainable resolution. Here we report general method for localized three-dimensional reconstruction such subunits. After determining particle orientations, local areas corresponding to be extracted and treated as single particles....
Abstract The Commander complex, a 16-protein assembly, plays multiple roles in cell homeostasis, cycle and immune response. It consists of copper-metabolism Murr1 domain proteins (COMMD1–10), coiled-coil domain-containing (CCDC22 CCDC93), DENND10 the Retriever subcomplex (VPS26C, VPS29 VPS35L), all expressed ubiquitously body linked to various diseases. Here, we report structure key interactions endogenous human complex by cryogenic-electron microscopy mass spectrometry-based proteomics....
Abstract Membranes in cells have defined distributions of lipids each leaflet, controlled by lipid scramblases and flip/floppases. However, for some intracellular membranes such as the endoplasmic reticulum (ER) not been identified. Members TMEM16 family either scramblase or chloride channel activity. Although TMEM16K is widely distributed associated with neurological disorder autosomal recessive spinocerebellar ataxia type 10 (SCAR10), its location cells, function structure are largely...
ABSTRACT Hantaviruses (family Bunyaviridae ) are rodent-borne emerging viruses that cause a serious, worldwide threat to human health. Hantavirus diseases include hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome. Virions enveloped contain tripartite single-stranded negative-sense RNA genome. Two types of glycoproteins, G N C , embedded in the viral membrane form protrusions, or “spikes.” The encloses ribonucleoprotein core, which consists segments, nucleocapsid...
ABSTRACT Rift Valley fever virus (RVFV) is a member of the genus Phlebovirus within family Bunyaviridae . It mosquito-borne zoonotic agent that can cause hemorrhagic in humans. The enveloped RVFV virions are known to be covered by capsomers glycoproteins G N and C , organized on T=12 icosahedral lattice. However, structural units forming have not been determined. Conflicting biochemical results for another phlebovirus (Uukuniemi virus) indicated existence either homodimers or -G heterodimers...
Although several different flaviviruses may cause encephalitis, Japanese encephalitis virus is the most significant, being responsible for thousands of deaths each year in Asia. The structural and molecular basis this not fully understood. Here, we report cryo-electron microscopy structure mature at near-atomic resolution, which reveals an unusual "hole" on surface, surrounded by five encephalitic-specific motifs implicated receptor binding. Glu138 E, highly conserved encephalitic...
Significance The negative-strand RNA viruses comprise several significant human, animal, and plant pathogens that have considerable health economic impact globally. During infection, replication of the single-stranded negative-sense genome occurs through a complementary intermediate, which is believed to complex with viral proteins form ribonucleoprotein (cRNP). isolation these complexes from infected cells has never been accomplished, greatly hampering our understanding replication. We...
Lassa virus is an enveloped, bi-segmented RNA and the most prevalent fatal of all Old World arenaviruses. Virus entry into host cell mediated by a tripartite surface spike complex, which composed two viral glycoprotein subunits, GP1 GP2, stable signal peptide. Of these, binds to cellular receptors GP2 catalyzes fusion between envelope membrane during endocytosis. The molecular structure conformational rearrangements induced low pH, prior fusion, remain poorly understood. Here, we analyzed...
Significance Lassa virus is a highly pathogenic arenavirus that causes severe hemorrhagic fever in humans. Currently, there are no efficacious vaccines or treatments available to combat this pathogen. An important component of any vaccine candidate against will likely include the glycosylated glycoprotein complex presented on virion surface. Here, we determine composition glycome, revealing presents an abundance glycans not biosynthetically processed full maturity. Such underprocessed form...
Measles virus is a highly infectious, enveloped, pleomorphic virus. We combined electron cryotomography with subvolume averaging and immunosorbent microscopy to characterize the 3D ultrastructure of virion. show that matrix protein forms helices coating helical ribonucleocapsid rather than inner leaflet membrane, as previously thought. The folded into tight bundles through matrix–matrix interactions. implications for assembly are already tightly interacts in cytoplasm, providing structural...
Significance Severe fever with thrombocytopenia syndrome virus (SFTSV) is a deadly tick-borne viral pathogen. Since first being reported in China 2009, SFTSV has spread throughout South Korea and Japan, mortality rates reaching up to 30%. The surface of the virion decorated by two glycoproteins, Gn Gc. Here, we report atomic-level structure Gc glycoprotein conformation formed during uptake into host cell. Our analysis reveals conformational changes that undergoes cell infection provides...
Abstract Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine–glycine–aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1. Infection can also occur tissue culture adapted absence acquired basic mutations interacting with heparin sulphate (HS); this is attenuated natural infections. HS interaction has been visualized at site two serotypes suggesting propensity for sulfated-sugar...
Abstract The integrity of a cell’s proteome depends on correct folding polypeptides by chaperonins. chaperonin TCP-1 ring complex (TRiC) acts as obligate folder for >10% cytosolic proteins, including he cytoskeletal proteins actin and tubulin. Although its architecture how it recognizes substrates are emerging from structural studies, the subsequent fate inside TRiC chamber is not defined. We trapped endogenous human with (actin, tubulin) cochaperone (PhLP2A) at different stages,...
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-located protein with cytoprotective effects in neurons and pancreatic β cells vitro models of neurodegeneration diabetes vivo. However, the exact mode MANF action has remained elusive. Here, we show that directly interacts ER transmembrane unfolded response (UPR) sensor IRE1α, identify binding interface between IRE1α. The expression wild-type MANF, but not its IRE1α binding-deficient mutant,...
Abstract Viral capsids can adopt various geometries, most iconically characterized by icosahedral or helical symmetries. Importantly, precise control over the size and shape of virus would have advantages in development new vaccines delivery systems. However, current tools to direct assembly process a programmable manner are exceedingly elusive. Here we introduce modular approach demonstrating DNA-origami-directed polymorphism single-protein subunit capsids. We achieve capsid shape, topology...
In January 2020, a workshop was held at EMBL-EBI (Hinxton, UK) to discuss data requirements for deposition and validation of cryoEM structures, with focus on single-particle analysis. The meeting attended by 45 experts in processing, model building refinement, validation, archiving such structures. This report describes the workshop's motivation history, topics discussed, consensus recommendations resulting from workshop. Some challenges future methods-development efforts this area are also...
mRNA is an important molecule in vaccine development and treatment of genetic disorders. Its capability to hybridize with DNA oligonucleotides a programmable manner facilitates the formation RNA-DNA origami structures, which can possess well-defined morphology serve as rigid supports for delivery. However, date, comprehensive studies on requirements efficient folding into distinct mRNA-DNA structures while preserving its translation functionality remain elusive. Here, impact design...
Bunyaviridae is a large family of viruses that have gained attention as "emerging viruses" because many members cause serious disease in humans, with an increasing number outbreaks. These negative-strand RNA possess membrane envelope covered by glycoproteins. The virions are pleiomorphic and thus not been amenable to structural characterization using common techniques involve averaging electron microscopic images. Here, we determined the three-dimensional structure member cryotomography....
Spatial organization of membranes into domains distinct protein and lipid composition is a fundamental feature biological systems. The plasma membrane organized in such to efficiently orchestrate the many reactions occurring there simultaneously. Despite almost universal presence domains, mechanisms their formation are often unclear. Yeast cells prominent domain organization, which at least partially mediated by eisosomes. Eisosomes large complexes that primarily composed subunits two...