A5027567346- Advanced NMR Techniques and Applications
- Protein Structure and Dynamics
- NMR spectroscopy and applications
- Advanced MRI Techniques and Applications
- Enzyme Structure and Function
- Molecular spectroscopy and chirality
- Spectroscopy and Quantum Chemical Studies
- Electron Spin Resonance Studies
- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- Mass Spectrometry Techniques and Applications
- Genomics and Chromatin Dynamics
- Heat shock proteins research
- Photosynthetic Processes and Mechanisms
- Lanthanide and Transition Metal Complexes
- Protein Kinase Regulation and GTPase Signaling
- DNA and Nucleic Acid Chemistry
- Biochemical and Molecular Research
- Endoplasmic Reticulum Stress and Disease
University of Toronto
2022-2024
Laboratoire des Biomolécules
2017-2023
École Normale Supérieure - PSL
2017-2023
University of Arizona
2018-2023
École Normale Supérieure
2020-2023
Sorbonne Université
2017-2022
Université Paris Sciences et Lettres
2017-2022
Centre National de la Recherche Scientifique
2017-2022
University of Massachusetts Amherst
2017
Epigenetic modifications of chromatin play a critical role in regulating the fidelity genetic code and controlling translation information into protein components cell. One key posttranslational modification is acetylation histone lysine residues. Molecular dynamics simulations, to smaller extent experiment, have established that increases tails. However, systematic, atomic resolution experimental investigation how this epigenetic mark, focusing on one at time, influences structural...
Abstract To achieve substrate specificity, protein phosphate 1 (PP1) forms holoenzymes with hundreds of regulatory and inhibitory proteins. Inhibitor-3 (I3) is an ancient inhibitor PP1 putative roles in maturation the regulation activity. Here, we show that I3 residues 27–68 are necessary sufficient for binding inhibition. In addition to a canonical RVxF motif, which shared by nearly all regulators inhibitors, non-canonical SILK also binds via multiple basic bind directly acidic groove,...
Nuclear magnetic resonance (NMR) relaxation experiments shine light onto the dynamics of molecular systems in picosecond to millisecond timescales. As these methods cannot provide an atomically resolved view motion atoms, functional groups, or domains giving rise such signals, techniques have been combined with (MD) simulations obtain mechanistic descriptions and gain insights into role side chain domain motion. In this work, we present a comparison five computational that permit joint...
Motions of proteins are essential for the performance their functions. Aliphatic protein side chains and motions play critical roles in interactions: recognition binding partner molecules at surface or serving as an entropy reservoir within hydrophobic core. Here, we present a new NMR method based on high-resolution relaxometry high-field relaxation to determine quantitatively both motional amplitudes time scales methyl-bearing picosecond-to-nanosecond range. We detect wide variety...
Many intrinsically disordered proteins (IDPs) and protein regions (IDRs) engage in transient, yet specific, interactions with a variety of partners. Often, if not always, partner lead to partial folding the IDR. Characterizing conformational space such complexes is challenging: solution-state NMR, signals IDR interacting region become broad, weak, often invisible, while X-ray crystallography only provides information on fully ordered regions. There thus need for simple method characterize...
NMR spectroscopy is an important tool for the measurement of electrostatic properties biomolecules. To this point, paramagnetic relaxation enhancements (PREs) 1H nuclei arising from nitroxide cosolutes in biomolecular solutions have been used to measure effective near-surface potentials (ϕENS) proteins and nucleic acids. Here, we present a gadolinium (Gd)-based method, exploiting Gd chelates with different net charges, measuring ϕENS values demonstrate its utility through applications number...
Nuclear magnetic relaxation provides invaluable quantitative site-specific information on the dynamics of complex systems. Determining nanosecond time scales requires measurements at low fields incompatible with high-resolution NMR. Here, we use a two-field NMR spectrometer to measure carbon-13 transverse and longitudinal rates field as 0.33 T (proton Larmor frequency 14 MHz) in specifically labeled side chains protein ubiquitin. The radiofrequency pulses enhances accuracy compared...
Nuclear Magnetic Resonance (NMR) is a tool of choice to characterize molecular motions. In biological macromolecules, pico- nanosecond motions, in particular, can be probed by nuclear spin relaxation rates, which depend on the time fluctuations orientations interaction frames. For past 40 years, rates have been successfully analyzed using Model-Free (MF) approach, makes no assumption nature motions and reports effective amplitude timescale However, obtaining mechanistic picture from this...
Nuclear magnetic relaxation is widely used to probe protein dynamics. For decades, most analyses of in proteins have relied successfully on the model-free approach, forgoing mechanistic descriptions motion. Model-free types correlation functions cannot describe a large carbon-13 dataset side chains. Here, we use molecular dynamics simulations design explicit models motion and solve Fokker-Planck diffusion equations. These provide better agreement with data, insight, direct link configuration entropy.
Abstract The dynamics of molecules in solution is usually quantified by the determination timescale-specific amplitudes motions. High-resolution nuclear magnetic resonance (NMR) relaxometry experiments—where sample transferred to low fields for longitudinal ( T 1 ) relaxation, and back high field detection with residue-specific resolution—seeks increase ability distinguish contributions from motion on timescales slower than a few nanoseconds. However, tumbling molecule masks some these...
The use of relaxation interference in the methyl Transverse Relaxation-Optimized SpectroscopY (TROSY) experiment has opened new avenues for study large proteins and protein assemblies nuclear magnetic resonance. So far, theoretical description methyl-TROSY been limited to slow-tumbling approximation, which is correct on high-field spectrometers. In a recent paper, favorable was observed groups small at field as low 0.33 T, well outside regime. Here, we present model describe over broad range...
Protein phosphatase 1 (PP1) dephosphorylates hundreds of key biological targets by associating with nearly 200 regulatory proteins to form highly specific holoenzymes. The vast majority regulators are intrinsically disordered (IDPs) and bind PP1 via short linear motifs within their regions. One the most ancient is SDS22, a protein that conserved from yeast mammals. Sequence analysis SDS22 revealed it leucine-rich repeat (LRR) protein, suggesting unlike every other known regulator, not an IDP...
Here we apply the detectors approach to probe amount of information in high-resolution relaxometry measurements biological macromolecules solution. We show that provides new relevant nanosecond range and additional is all more large as overall rotational diffusion slow.
Nuclear magnetic relaxation is widely used to probe protein dynamics. For decades, most analyses of in proteins have relied successfully on the model-free approach, forgoing mechanistic descriptions motions. Model-free types correlation functions cannot describe a large carbon-13 dataset sidechains. Here, we use molecular dynamics simulations design explicit models motion and solve Fokker-Planck diffusion equations. These provide better agreement with data, insight direct link configuration entropy.
Biomolecular NMR spectroscopy has greatly benefited from the development of TROSY-type pulse sequences, in pair with specific labeling. The selection spin operators favorable relaxation properties led to an increase resolution and sensitivity spectra large biomolecules. However, nuclei a chemical shift anisotropy (CSA) contribution can still suffer linewidths at conventional magnetic fields (higher than 9 T). Here, we introduce concept two-field TROSY (2F-TROSY) where shifts CSA is labeled...
Relaxometry consists in measuring relaxation rates over orders of magnitude magnetic fields to probe motions complex systems. High-resolution relaxometry (HRR) experiments can be performed on conventional high-field NMR magnets equipped with a sample shuttle. During the experiment, shuttle transfers between center and chosen position stray field for during variable delay, thus using as field. As delay occurs outside probe, HRR cannot rely control cross-relaxation pathways, which is standard...
Relaxometry consists in measuring relaxation rates over orders of magnitude magnetic fields to probe motions complex systems. High-resolution relaxometry (HRR) experiments can be performed on conventional high-field NMR magnets equipped with a sample shuttle. During the experiment, shuttle transfers between center and chosen position stray field for during variable delay, thus using as field. As delay occurs outside probe, HRR cannot rely control cross-relaxation pathways, which is standard...