A5038061386- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Protein Structure and Dynamics
- Enzyme Structure and Function
- HIV Research and Treatment
- DNA and Nucleic Acid Chemistry
- HIV/AIDS drug development and treatment
- Advanced biosensing and bioanalysis techniques
- Glycosylation and Glycoproteins Research
- RNA Interference and Gene Delivery
- Bacterial Genetics and Biotechnology
- CRISPR and Genetic Engineering
- Mass Spectrometry Techniques and Applications
- Peptidase Inhibition and Analysis
- Viral Infectious Diseases and Gene Expression in Insects
- Genomics and Chromatin Dynamics
- Endoplasmic Reticulum Stress and Disease
- Chemical Synthesis and Analysis
- Microtubule and mitosis dynamics
- Copper Interconnects and Reliability
- Bacteriophages and microbial interactions
- Ubiquitin and proteasome pathways
- Cellular transport and secretion
- Cancer-related gene regulation
Center for Cancer Research
2016-2025
National Cancer Institute
2016-2025
Frederick National Laboratory for Cancer Research
2009-2025
National Institutes of Health
2014-2023
National Cancer Institute
2020-2022
Huazhong Agricultural University
2013
Advanced Photon Source
2009
Center for Information Technology
2008
Argonne National Laboratory
2008
University of Maryland, Baltimore
2007
Abstract RNA flexibility is reflected in its heterogeneous conformation. Through direct visualization using atomic force microscopy (AFM) and the adenosylcobalamin riboswitch aptamer domain as an example, we show that a single sequence folds into conformationally architecturally structures under near-physiological solution conditions. Recapitulated 3D topological from AFM molecular surfaces reveal all conformers share same secondary structural elements. Only population-weighted cohort, not...
Crystal structures have shown that the HIV-1 protease flaps, domains control access to active site, are closed when site is occupied by a ligand. Although flap ranging from semi-open observed in free protease, crystal reveal even flaps block indicating mobile solution. The goals of this paper characterize secondary structure and fast (sub-ns) dynamics solution, relate these results X-ray compare them with predictions calculations. To end we obtained nearly complete backbone many sidechain...
Histone modifications and DNA methylation represent two layers of heritable epigenetic information that regulate eukaryotic chromatin structure gene activity. UHRF1 is a unique factor bridges these layers; it required for maintenance at hemimethylated CpG sites, which are specifically recognized through its SRA domain also interacts with histone H3 trimethylated on lysine 9 (H3K9me3) in an unspecified manner. Here we show contains tandem Tudor (TTD) recognizes tail peptides the...
In order to improve the design of HIV-1 protease inhibitors, it is essential understand how they interact with active site residues, particularly catalytic Asp25 and Asp125 residues. KNI-272 a promising, potent inhibitor (Ki ≈ 5 pM), currently undergoing phase 1 clinical trials. Because asymmetric, complex forms homodimeric also lacks symmetry, two monomers can have distinct NMR spectra. Monomer specific signal assignments were obtained for amino acid residues in drug binding as well six...
The 3 ′ untranslated region (3 UTR) of turnip crinkle virus (TCV) genomic RNA contains a cap-independent translation element (CITE), which includes ribosome-binding structural (RBSE) that participates in recruitment the large ribosomal subunit. In addition, symmetric loop RBSE plays key role coordinating incompatible processes viral and replication, require enzyme progression opposite directions on template. To understand basis for subunit intricate interplay among different parts molecule,...
The copper-sensing operon repressor (CsoR) is representative of a major Cu(I)-sensing family bacterial metalloregulatory proteins that has evolved to prevent cytoplasmic copper toxicity. It unknown how Cu(I) binding tetrameric CsoRs mediates transcriptional derepression resistance genes. A phylogenetic analysis 227 DUF156 protein members, including biochemically or structurally characterized CsoR/RcnR repressors, reveals Geobacillus thermodenitrificans (Gt) CsoR here from pathogenic bacilli...
MicroRNA (miRNA) processing begins with Drosha cleavage, the fidelity of which is critical for downstream and mature miRNA target specificity. To understand how pri-miRNA sequence structure influence we studied maturation three pri-miR-9 paralogs, encode same but differ in surrounding scaffold. We show that pri-miR-9-1 has a unique cleavage profile due to its distorted flexible stem structure. Cleavage pri-miR-9-1, not pri-miR-9-2 or pri-miR-9-3, generates an alternative miR-9 shifted seed...
Abstract Synthetic RNA devices are engineered to control gene expression and offer great potential in both biotechnology clinical applications. Here, we present multidisciplinary structural biochemical data for a tetracycline (Tc)-responsive device (D43) ligand-free bound states, providing structure-dynamical basis signal transmission. Activation of self-cleavage is achieved via ligand-induced conformational dynamical changes that stabilize the elongated bridging helix harboring...
Human ubiquitin-specific cysteine protease 5 (USP5, also known as ISOT and isopeptidase T), an 835-residue multidomain enzyme, recycles ubiquitin by hydrolyzing isopeptide bonds in a variety of unanchored polyubiquitin substrates. Activation the enzyme's hydrolytic activity toward ubiquitin-AMC (7-amino-4-methylcoumarin), fluorogenic substrate, addition free, monoubiquitin suggested allosteric mechanism activation ZnF-UBP domain (residues 163–291), which binds substrate's diglycine carboxyl...
The cell is constructed by higher-order structures and organelles through complex interactions among distinct structural constituents. centrosome a membraneless organelle composed of two microtubule-derived called centrioles an amorphous mass pericentriolar material. Super-resolution microscopic analyses in various organisms revealed that diverse material proteins are concentrically localized around centriole highly organized manner. However, the molecular nature underlying these...
RNA molecules are functionally dynamic, even for the well-folded structures. Full mapping of conformational space in solution is one unmet challenges. We have developed a new approach direct visualization and 3D topological structure determination individual conformers under relevant to physiological condition using atomic force microscopy neural networks. The populations consistent with ensemble measurements such as small angle X-ray scattering. Our makes it possible study dynamics...
Abstract The three‐dimensional solution structure of the HIV‐1 protease homodimer, MW 22.2 kDa, complexed to a potent, cyclic urea‐based inhibitor, DMP323, is reported. This first an HIV protease/inhibitor complex that has been elucidated. Multidimensional heteronuclear NMR spectra were used assemble more than 4,200 distance and angle constraints. Using constraints, together with hybrid geometry/simulated annealing protocol, ensemble 28 structures was calculated having no or violations...
Determining the global architecture of multicomponent systems is a central problem in understanding biomacromolecular machines. Defining interfaces among components and structure biological interactions on molecular level. We demonstrate that solution X-ray scattering data can be used to precisely determine intermolecular from just subunit structures, complete absence NMR restraints using an example 30 kDa RNA−RNA complex. The backbone root-mean-square deviation (rmsd) between structures are...
Determining architectures of multicomponent proteins or protein complexes in solution is a challenging problem. Here we report methodology that simultaneously uses residual dipolar couplings (RDC) and the small-angle X-ray scattering (SAXS) restraints to mutually orient subunits define global shape complexes. Our implemented an efficient algorithm demonstrated using five examples. First, demonstrate general approach with simulated data for HIV-1 protease, globular homodimeric protein....