A5000095767- Photosynthetic Processes and Mechanisms
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Photoreceptor and optogenetics research
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Spectroscopy and Quantum Chemical Studies
- Electron Spin Resonance Studies
- Hemoglobin structure and function
- Enzyme Structure and Function
- Bacterial Genetics and Biotechnology
- Metabolism and Genetic Disorders
- DNA and Nucleic Acid Chemistry
- Coenzyme Q10 studies and effects
- Biochemical and Molecular Research
- Electrochemical sensors and biosensors
- Tuberculosis Research and Epidemiology
- Origins and Evolution of Life
- Epigenetics and DNA Methylation
- Evolution and Genetic Dynamics
- Fluid Dynamics and Heat Transfer
- Electrochemical Analysis and Applications
- Surface Modification and Superhydrophobicity
- Genetics, Aging, and Longevity in Model Organisms
- Monoclonal and Polyclonal Antibodies Research
National Institute of Technology Patna
2025
University of Helsinki
2013-2024
Helsinki Institute of Physics
2017-2024
Czech Academy of Sciences, Institute of Biotechnology
2018-2024
University of Pennsylvania
2024
Biocenter Finland
2023
GLA University
2021-2022
International Centre for Genetic Engineering and Biotechnology
2022
Shyam Shah Medical College
2022
Mathrusri Ramabai Ambedkar Dental College & Hospital
2022
Homodimeric class I cytokine receptors are assumed to exist as preformed dimers that activated by ligand-induced conformational changes. We quantified the dimerization of three prototypic in plasma membrane living cells single-molecule fluorescence microscopy. Spatial and spatiotemporal correlation individual receptor subunits showed revealed associated Janus kinase 2 (JAK2) dimerizes through its pseudokinase domain. Oncogenic hyperactive JAK2 mutants promoted ligand-independent...
Abstract Mitochondrial energy conversion requires an intricate architecture of the inner mitochondrial membrane 1 . Here we show that a supercomplex containing all four respiratory chain components contributes to curvature induction in ciliates. We report cryo-electron microscopy and cryo-tomography structures comprises 150 different proteins 311 bound lipids, forming stable 5.8-MDa assembly. Owing subunit acquisition extension, complex I associates with IV dimer, generating wedge-shaped gap...
Respiratory complex I is a redox-driven proton pump, accounting for large part of the electrochemical gradient that powers mitochondrial adenosine triphosphate synthesis. Complex dysfunction associated with severe human diseases. Assembly one-megadalton in inner membrane requires assembly factors and chaperones. We have determined structure from aerobic yeast Yarrowia lipolytica by electron cryo-microscopy at 3.2-Å resolution. A ubiquinone molecule was identified access path to active site....
Significance Complex I is a redox-driven proton pump, central for aerobic energy transduction. We show here by large-scale quantum and classical molecular simulations how reduction of quinone (Q) in the hydrophilic domain complex activates pump membrane domain. Our indicate that Q leads to local charge redistributions trigger conformational changes via an array alternating charged residues domain, nearly 40 Å away. These mechanistic observations are supported site-directed mutagenesis key...
Significance Complex I is the primary energy-converting enzyme of aerobic respiratory chains. By reducing quinone to quinol, this gigantic pumps protons across its membrane domain, which in turn powers ATP synthesis and active transport. Despite recently resolved molecular structures complex I, dynamics coupling pumping function remains unclear. Here we show by large-scale simulations that reduction leads ejection quinol molecule from site into a second binding near proton-pumping domain I....
Mitochondrial NADH:ubiquinone oxidoreductase (complex I) is a 1-MDa membrane protein complex with central role in energy metabolism. Redox-driven proton translocation by I contributes substantially to the motive force that drives ATP synthase. Several structures of from bacteria and mitochondria have been determined, but its catalytic mechanism has remained controversial. We here present cryo-EM structure Yarrowia lipolytica at 2.1-Å resolution, which reveals positions more than 1600...
Classical molecular dynamics (MD) simulations provide unmatched spatial and time resolution of protein structure function. However, the accuracy MD often depends on quality force field parameters scale sampling. Another limitation conventional is that protonation states titratable amino acid residues remain fixed during simulations, even though state changes coupled to conformational are central Due uncertainty in selecting states, classical sometimes performed with all acids modeled their...
In bacteria, the majority of exported proteins are translocated by Sec system, which recognizes signal sequence a preprotein and uses ATP proton motive force to mediate protein translocation across cytoplasmic membrane. SecA is an essential component this containing molecular motor that facilitates translocation. Here we report three-dimensional structure Mycobacterium tuberculosis . Each subunit homodimer contains “motor” domain domain. The predicts can interact with SecYEG pore function as...
VlsE is an outer surface lipoprotein of<i>Borrelia burgdorferi</i> that undergoes antigenic variation through elaborate gene conversion mechanism and thought to play a major role in the immune response Lyme disease borellia. The crystal structure of recombinant variant protein VlsE1 at 2.3-Å resolution reveals six variable regions form loop structures constitute most membrane distal VlsE, covering predominantly α-helical, invariant protein. localization amino acid segments appears protect...
Respiratory complex I is a redox-driven proton pump. Several high-resolution structures of have been determined providing important information about the putative transfer paths and conformational transitions that may occur during catalysis. However, how redox energy coupled to pumping protons remains unclear. In this article, we review biochemical, structural molecular simulation data on discuss several coupling models, including key unresolved mechanistic questions. Focusing both...
Significance Classical atomistic molecular dynamics simulations and free-energy calculations performed on cytochrome c oxidase in an explicit membrane–solvent environment show that the water molecules nonpolar cavity near active site of oxygen reduction reorientate according to redox state enzyme, guiding path proton transfer thereby effectively preventing short-circuit pump. The results highlight important role protein-bound biological energy conversion––a notion shared with...
Significance Density functional theory studies on the O H state in catalytic mechanism of cytochrome c oxidase are performed. The proposed structure and its calculated characteristics found to comply with experimental data. presented hypothesis solves, at least part, dilemma states oxidase.
Abstract Membrane bound respiratory complex I is the key enzyme in chains of bacteria and mitochondria, couples reduction quinone to pumping protons across membrane. Recently solved crystal or electron microscopy structures bacterial mitochondrial complexes have provided significant insights into proton transfer pathways. However, due large spatial separation between routes, molecular mechanism coupling remains unclear. Here, based on atomistic dynamics simulations performed entire structure...
Respiratory complex I performs the reduction of quinone (Q) to quinol (QH2) and pumps protons across membrane. Structural data on have provided spectacular insights into electron proton transfer paths, as well long (~30 Å) unique substrate binding channel. However, due missing structural information Q modes, it remains unclear how drives range (~20 nm) redox-coupled pumping in I. Here we applied multiscale computational approaches study dynamics redox chemistry QH2. Based tens microseconds...
Abstract Respiratory complex I catalyzes electron transfer from NADH to ubiquinone (Q) coupled vectorial proton translocation across the inner mitochondrial membrane. Despite recent progress in structure determination of this very large membrane protein complex, coupling mechanism is a matter ongoing debate and function accessory subunits surrounding canonical core essentially unknown. Concerted rearrangements within cluster conserved loops central NDUFS2 (β1-β2 S2 loop), ND1 (TMH5-6 loop)...
The outer surface protein C (OspC) is one of the major host-induced antigens Borrelia burgdorferi, causative agent Lyme disease. We have solved crystal structure recombinant OspC to a resolution 2.5 A. OspC, largely alpha-helical protein, dimer with characteristic central four-helical bundle formed by association two longest helices from each subunit. very different OspA and similar extracellular domain bacterial aspartate receptor variant glycoprotein Trypanosoma brucei. Most...
The N-1-(5′-phosphoribosyl)-ATP transferase catalyzes the first step of histidine biosynthetic pathway and is regulated by a feedback mechanism product histidine. crystal structures theN-1-(5′-phosphoribosyl)-ATP fromMycobacterium tuberculosis in complex with inhibitor AMP has been determined to 1.8 Å resolution without ligands 2.7 resolution. active enzyme exists primarily as dimer, histidine-inhibited form hexamer. structure represents new fold for phosphoribosyltransferase, consisting...