A5012871855- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- Cardiovascular Function and Risk Factors
- RNA and protein synthesis mechanisms
- Muscle Physiology and Disorders
- Escherichia coli research studies
- Biochemical and Structural Characterization
- Advanced Electron Microscopy Techniques and Applications
- RNA regulation and disease
- RNA Research and Splicing
- Photosynthetic Processes and Mechanisms
- Lysosomal Storage Disorders Research
- Streptococcal Infections and Treatments
- Trypanosoma species research and implications
- Microtubule and mitosis dynamics
- Microfluidic and Bio-sensing Technologies
- Infant Nutrition and Health
- Bacteriophages and microbial interactions
- Cellular Mechanics and Interactions
- Nanofabrication and Lithography Techniques
- Research on Leishmaniasis Studies
Boston University
2020-2025
Boston VA Research Institute
2022-2025
Harvard University
2022-2025
Following binding to the thin filament, β-cardiac myosin couples ATP-hydrolysis conformational rearrangements in motor that drive myofilament sliding and cardiac ventricular contraction. However, key features of cardiac-specific actin-myosin interaction remain uncertain, including structural effect ADP release from myosin, which is rate-limiting during force generation. In fact, slows under experimental load or intact heart due afterload, thereby adjusting muscle power output meet...
Previous studies aimed at defining the mechanistic basis of hypertrophic cardiomyopathy caused by A331P cardiac actin have reported conflicting results. The mutation is located along an surface strand, proximal to residues that interact with tropomyosin. These F-actin-tropomyosin associations are vital for proper contractile inhibition. To help resolve disease pathogenesis, we implemented a multidisciplinary approach. Transgenic Drosophila, expressing actin, displayed skeletal muscle...
The movement and pathogenicity of trypanosomatid species, the causative agents trypanosomiasis leishmaniasis, are dependent on a flagellum that contains an axoneme dynein-bound doublet microtubules (DMTs). In this work, we present cryo–electron microscopy structures DMTs from two Leishmania tarentolae Crithidia fasciculata , at resolutions up to 2.7 angstrom. revealed 27 trypanosomatid-specific microtubule inner proteins, specialized dynein-docking complex, presence paralogous proteins...
During force-generating steps of the muscle crossbridge cycle, tip myosin motor, specifically loop-4, contacts tropomyosin cable actin filaments. In current study, we determined corresponding effect loop-4 on regulatory positioning actin. To accomplish this, compared high-resolution cryo-EM structures S1-decorated thin filaments containing either wild-type or a mutant construct, where seven-residue portion that was replaced by glycine residues, thus removing polar side chains from residues...
Bacterial adhesion pili are key virulence factors that mediate host-pathogen interactions in diverse epithelial environments. Deploying a multimodal approach, we probed the structural basis underpinning biophysical properties of originating from enterotoxigenic (ETEC) and uropathogenic bacteria. Using cryo-electron microscopy solved structures three vaccine target ETEC bacteria, CFA/I, CS17, CS20. Pairing these previous pilus with force spectroscopy steered molecular dynamics simulations,...
The axoneme, a microtubule-based array at the center of every cilium, has been subject structural investigations for decades, but only recent advances in cryo-EM and cryo-ET have allowed molecular-level interpretation entire complex to be achieved. unique properties nine doublet microtubules central pair singlet that form including highly decorated tubulin lattice docking massive axonemal complexes, provide opportunities challenges sample preparation, 3D reconstruction atomic modeling. Here,...
Translation initiation in eukaryotes requires multiple eukaryotic translation factors (eIFs) and involves continuous remodeling of the ribosomal preinitiation complex (PIC). The GTPase eIF2 brings initiator Met-tRNAi to PIC. Upon start codon selection GTP hydrolysis promoted by its GTPase-activating protein (GAP) eIF5, eIF2-GDP is released with eIF5. It not known how eIF5 dissociates from other binding partners leave PIC only eIF2. Here, we report that two intrinsically disordered regions...
Haemophilus influenza is an invasive species known to cause meningitis, pneumonia, and other serious infections in young children immunosuppressed individuals.The most prevalent type H. B (Hib), a gram-negative bacterium that colonizes the human nasopharynx [3].The surface of Hib bacteria contains filamentous pili are key bacterial binding colonization mucosal cells (e.g.[7]).Although vital for pathogenicity Hib, molecular structure has not been resolved high resolution.With aim solving...
Cardiac muscle contraction occurs when thin filaments slide past thick driven by the action of molecular motor, myosin.Projecting from filaments, myosin heads bind to filament actin and undergo ATPase-associated conformational changes propel move one another.Tropomyosin, a coiled-coil protein that wraps around as continuous cable, regulates this process sterically controlling myosin's ability actin.Although several actomyosin structures have been proposed, structure describing cardiac...
Abstract Following binding to the thin filament, β-cardiac myosin couples ATP-hydrolysis conformational rearrangements in motor that drive myofilament sliding and cardiac ventricular contraction. However, key features of cardiac-specific actin-myosin interaction remain uncertain, including structural effect ADP release from myosin, which is ratelimiting during force generation. In fact, slows under experimental load or intact heart due afterload, thereby adjusting muscle power output meet...
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