Lewis E Kay
University of Toronto
H-index: 139
North America-Canada
Description
Lewis E Kay, With an exceptional h-index of 139 and a recent h-index of 62 (since 2020), a distinguished researcher at University of Toronto,
His recent articles reflect a diverse array of research interests and contributions to the field:
Design of amyloidogenic peptide traps
Exploring Host–Guest Interactions within a 600 kDa DegP Protease Cage Complex Using Hydrodynamics Measurements and Methyl-TROSY NMR
Optimization of TROSY-and anti-TROSY-based 15N CPMG relaxation dispersion experiments through phase cycling
Poly (ADP-ribosyl) ation enhances nucleosome dynamics and organizes DNA damage repair components within biomolecular condensates
A delayed decoupling methyl-TROSY pulse sequence for atomic resolution studies of folded proteins and RNAs in condensates
Cryo-EM of the Nucleosome Core Particle Bound to Ran-RCC1 Reveals a Dynamic Complex
Practical considerations for the measurement of near-surface electrostatics based on solvent paramagnetic relaxation enhancements
Flexible client-dependent cages in the assembly landscape of the periplasmic protease-chaperone DegP
Professor Information
University | University of Toronto |
---|---|
Position | ___ |
Citations(all) | 77157 |
Citations(since 2020) | 14112 |
Cited By | 71545 |
hIndex(all) | 139 |
hIndex(since 2020) | 62 |
i10Index(all) | 449 |
i10Index(since 2020) | 280 |
University Profile Page | University of Toronto |
Top articles of Lewis E Kay
Design of amyloidogenic peptide traps
Segments of proteins with high β-strand propensity can self-associate to form amyloid fibrils implicated in many diseases. We describe a general approach to bind such segments in β-strand and β-hairpin conformations using de novo designed scaffolds that contain deep peptide-binding clefts. The designs bind their cognate peptides in vitro with nanomolar affinities. The crystal structure of a designed protein−peptide complex is close to the design model, and NMR characterization reveals how the peptide-binding cleft is protected in the apo state. We use the approach to design binders to the amyloid-forming proteins transthyretin, tau, serum amyloid A1 and amyloid β1−42 (Aβ42). The Aβ binders block the assembly of Aβ fibrils as effectively as the most potent of the clinically tested antibodies to date and protect cells from toxic Aβ42 species.
Authors
Danny D Sahtoe,Ewa A Andrzejewska,Hannah L Han,Enrico Rennella,Matthias M Schneider,Georg Meisl,Maggie Ahlrichs,Justin Decarreau,Hannah Nguyen,Alex Kang,Paul Levine,Mila Lamb,Xinting Li,Asim K Bera,Lewis E Kay,Tuomas PJ Knowles,David Baker
Journal
Nature Chemical Biology
Published Date
2024/3/19
Exploring Host–Guest Interactions within a 600 kDa DegP Protease Cage Complex Using Hydrodynamics Measurements and Methyl-TROSY NMR
The DegP protease-chaperone operates within the periplasm of Gram-negative bacteria, where it assists in the regulation of protein homeostasis, promotes virulence, and is essential to survival under stress. To carry out these tasks, DegP forms a network of preorganized apo oligomers that facilitate the capture of substrates within distributions of cage-like complexes which expand to encapsulate clients of various sizes. Although the architectures of DegP cage complexes are well understood, little is known about the structures, dynamics, and interactions of client proteins within DegP cages and the relationship between client structural dynamics and function. Here, we probe host–guest interactions within a 600 kDa DegP cage complex throughout the DegP activation cycle using a model α-helical client protein through a combination of hydrodynamics measurements, methyl-transverse relaxation optimized …
Authors
Robert W Harkness,Huaying Zhao,Yuki Toyama,Peter Schuck,Lewis E Kay
Journal
Journal of the American Chemical Society
Published Date
2024/3/13
Optimization of TROSY-and anti-TROSY-based 15N CPMG relaxation dispersion experiments through phase cycling
CPMG relaxation dispersion studies of biomolecular dynamics on the μs–ms timescale can provide detailed kinetic, thermodynamic, and structural insights into function. Frequently, the 15N spin serves as the probe of choice, as uniform incorporation of the 15N isotope is facile and cost-effective, and the interpretation of the resulting data is often relatively straightforward. In conventional CPMG relaxation dispersion experiments the application of CPMG pulses with constant radiofrequency (RF) phase can lead to artifactual dispersion profiles that result from off-resonance pulses, RF field inhomogeneity, and pulse miscalibration. The development of CPMG experiments with the [0013]-phase cycle has significantly reduced the impact of pulse imperfections over a greater bandwidth of frequency offsets in comparison to constant phase experiments. Application of 15N-TROSY-based CPMG schemes to studies of the …
Authors
Yingxian Cui,Yangzhuoyue Jin,Yu Hou,Xiaoxu Han,Haiyan Cao,Lewis E Kay,Tairan Yuwen
Journal
Journal of Magnetic Resonance
Published Date
2024/2/2
Poly (ADP-ribosyl) ation enhances nucleosome dynamics and organizes DNA damage repair components within biomolecular condensates
Nucleosomes, the basic structural units of chromatin, hinder recruitment and activity of various DNA repair proteins, necessitating modifications that enhance DNA accessibility. Poly(ADP-ribosyl)ation (PARylation) of proteins near damage sites is an essential initiation step in several DNA-repair pathways; however, its effects on nucleosome structural dynamics and organization are unclear. Using NMR, cryoelectron microscopy (cryo-EM), and biochemical assays, we show that PARylation enhances motions of the histone H3 tail and DNA, leaving the configuration of the core intact while also stimulating nuclease digestion and ligation of nicked nucleosomal DNA by LIG3. PARylation disrupted interactions between nucleosomes, preventing self-association. Addition of LIG3 and XRCC1 to PARylated nucleosomes generated condensates that selectively partition DNA repair-associated proteins in a PAR- and …
Authors
Michael L Nosella,Tae Hun Kim,Shuya Kate Huang,Robert W Harkness,Monica Goncalves,Alisia Pan,Maria Tereshchenko,Siavash Vahidi,John L Rubinstein,Hyun O Lee,Julie D Forman-Kay,Lewis E Kay
Journal
Molecular Cell
Published Date
2024/2/1
A delayed decoupling methyl-TROSY pulse sequence for atomic resolution studies of folded proteins and RNAs in condensates
Solution NMR spectroscopy has tremendous potential for providing atomic resolution insights into the interactions between proteins and nucleic acids partitioned into condensed phases of phase-separated systems. However, the highly viscous nature of the condensed phase challenges applications, and in particular, the extraction of quantitative, site-specific information. Here, we present a delayed decoupling-based HMQC pulse sequence for methyl-TROSY studies of ‘client’ proteins and nucleic acids partitioned into ‘scaffold’ proteinaceous phase-separated solvents. High sensitivity and excellent quality spectra are recorded of a nascent form of superoxide dismutase and of a small RNA fragment partitioned into CAPRIN1 condensates.
Authors
Rashik Ahmed,Atul K Rangadurai,Lisa Ruetz,Martin Tollinger,Christoph Kreutz,Lewis E Kay
Journal
Journal of Magnetic Resonance
Published Date
2024/5/1
Cryo-EM of the Nucleosome Core Particle Bound to Ran-RCC1 Reveals a Dynamic Complex
Ras-related nuclear protein (Ran) is a member of the Ras superfamily of small guanosine triphosphatases (GTPases) and a regulator of multiple cellular processes. In healthy cells, the GTP-bound form of Ran is concentrated at chromatin, creating a Ran•GTP gradient that provides the driving force for nucleocytoplasmic transport, mitotic spindle assembly, and nuclear envelope formation. The Ran•GTP gradient is maintained by the regulator of chromatin condensation 1 (RCC1), a guanine nucleotide exchange factor that accelerates GDP/GTP exchange in Ran. RCC1 interacts with nucleosomes, which are the fundamental repeating units of eukaryotic chromatin. Here, we present a cryo-EM analysis of a trimeric complex composed of the nucleosome core particle (NCP), RCC1, and Ran. While the contacts between RCC1 and Ran in the complex are preserved compared with a previously determined structure of …
Authors
Shuya Kate Huang,John L Rubinstein,Lewis E Kay
Journal
Biochemistry
Published Date
2024/3/19
Practical considerations for the measurement of near-surface electrostatics based on solvent paramagnetic relaxation enhancements
Electrostatic interactions can play important roles in regulating various biological processes. Quantifying surface electrostatics of biomolecules is, therefore, of significant interest. Recent advances in solution NMR spectroscopy have enabled site-specific measurements of de novo near-surface electrostatic potentials (ϕENS) based on a comparison of solvent paramagnetic relaxation enhancements generated from differently charged paramagnetic co-solutes with similar structures. Although the NMR-derived near-surface electrostatic potentials have been shown to agree with theoretical calculations in the context of folded proteins and nucleic acids, such benchmark comparisons may not always be possible, particularly in cases where high-resolution structural models are lacking, such as in the study of intrinsically disordered proteins. Cross-validation of ϕENS potentials can be achieved by comparing values …
Authors
Atul Kaushik Rangadurai,Yuki Toyama,Lewis E Kay
Journal
Journal of Magnetic Resonance
Published Date
2023/4/1
Flexible client-dependent cages in the assembly landscape of the periplasmic protease-chaperone DegP
The periplasmic protein DegP, which is implicated in virulence factor transport leading to pathogenicity, is a bi-functional protease and chaperone that helps to maintain protein homeostasis in Gram-negative bacteria and is essential to bacterial survival under stress conditions. To perform these functions, DegP captures clients inside cage-like structures, which we have recently shown to form through the reorganization of high-order preformed apo oligomers, consisting of trimeric building blocks, that are structurally distinct from client-bound cages. Our previous studies suggested that these apo oligomers may allow DegP to encapsulate clients of various sizes under protein folding stresses by forming ensembles that can include extremely large cage particles, but how this occurs remains an open question. To explore the relation between cage and substrate sizes, we engineered a series of DegP clients of increasing …
Authors
Robert W Harkness,Zev A Ripstein,Justin M Di Trani,Lewis E Kay
Journal
Journal of the American Chemical Society
Published Date
2023/6/7
Professor FAQs
What is Lewis E Kay's h-index at University of Toronto?
The h-index of Lewis E Kay has been 62 since 2020 and 139 in total.
What are Lewis E Kay's top articles?
The articles with the titles of
Design of amyloidogenic peptide traps
Exploring Host–Guest Interactions within a 600 kDa DegP Protease Cage Complex Using Hydrodynamics Measurements and Methyl-TROSY NMR
Optimization of TROSY-and anti-TROSY-based 15N CPMG relaxation dispersion experiments through phase cycling
Poly (ADP-ribosyl) ation enhances nucleosome dynamics and organizes DNA damage repair components within biomolecular condensates
A delayed decoupling methyl-TROSY pulse sequence for atomic resolution studies of folded proteins and RNAs in condensates
Cryo-EM of the Nucleosome Core Particle Bound to Ran-RCC1 Reveals a Dynamic Complex
Practical considerations for the measurement of near-surface electrostatics based on solvent paramagnetic relaxation enhancements
Flexible client-dependent cages in the assembly landscape of the periplasmic protease-chaperone DegP
...
are the top articles of Lewis E Kay at University of Toronto.
What is Lewis E Kay's total number of citations?
Lewis E Kay has 77,157 citations in total.