A5084357274- Protein Structure and Dynamics
- Advanced biosensing and bioanalysis techniques
- Wnt/β-catenin signaling in development and cancer
- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Radioactive element chemistry and processing
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Mass Spectrometry Techniques and Applications
- Drug Transport and Resistance Mechanisms
- Trace Elements in Health
- Lipid Membrane Structure and Behavior
- Cancer, Hypoxia, and Metabolism
- Chromium effects and bioremediation
- Advanced NMR Techniques and Applications
- Ion channel regulation and function
- thermodynamics and calorimetric analyses
- Genomics and Rare Diseases
- Evolution and Genetic Dynamics
- Medical Imaging Techniques and Applications
- Mine drainage and remediation techniques
- Chemical Synthesis and Characterization
- Boron Compounds in Chemistry
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
Invitae (United States)
2022-2024
Swarthmore College
2011-2023
University of California, San Francisco
2020-2023
Harvard University
2015-2019
The remarkable selectivity of N -methyl mesoporphyrin IX (NMM) for G-quadruplexes (GQs) is long known, however its ability to stabilize and bind GQs has not been investigated in detail. Through the use circular dichroism, UV-visible spectroscopy fluorescence resonance energy transfer (FRET) melting assay we have shown that NMM stabilizes human telomeric DNA dAG 3 (TTAG ) (Tel22) selective parallel conformation which it binds 1:1 stoichiometry with a binding constant ∼1.0 × 10 5 M −1 . does...
N-methyl mesoporphyrin IX (NMM) is exceptionally selective for G-quadruplexes (GQ) relative to duplex DNA and, as such, has found a wide range of applications in biology and chemistry. In addition, NMM parallel versus antiparallel GQ folds, was recently demonstrated our laboratory. Here, we present the X-ray crystal structure complex between human telomeric dAGGG(TTAGGG)(3), Tel22, determined two space groups, P2(1)2(1)2 P6, at 1.65 2.15 Å resolution, respectively. The former highest...
Guanine quadruplexes ( GQ ) are four‐stranded DNA structures formed by guanine‐rich sequences. The formation of GQs inhibits cancer cell growth, although the detection s in vivo has proven difficult, part because their structural diversity. development ‐selective fluorescent reporters would enhance our ability to quantify number and location s, ultimately advancing biological studies quadruplex relevance function. N ‐methylmesoporphyrin IX NMM interacts selectively with parallel‐stranded s;...
Nramp family transporters—expressed in organisms from bacteria to humans—enable uptake of essential divalent transition metals via an alternating-access mechanism that also involves proton transport. We present high-resolution structures Deinococcus radiodurans (Dra)Nramp multiple conformations provide a thorough description the transport cycle by identifying key intramolecular rearrangements and changes metal coordination sphere. Strikingly, while requires cycling outward- inward-open...
The C-C motif chemokine receptor 8 (CCR8) is a class A G-protein coupled that has emerged as promising therapeutic target in cancer. Targeting CCR8 with an antibody appeared to be attractive approach, but the molecular basis for chemokine-mediated activation and antibody-mediated inhibition of are not fully elucidated. Here, we obtain antagonist against human determine structures complex either or endogenous agonist ligand CCL1. Our studies reveal characteristic features allowing recognition...
Protocadherins (Pcdhs) are cell adhesion and signaling proteins used by neurons to develop maintain neuronal networks, relying on trans homophilic interactions between their extracellular cadherin (EC) repeat domains. We present the structure of antiparallel EC1-4 homodimer human PcdhγB3, a member γ subfamily clustered Pcdhs. Structure sequence comparisons α, β, Pcdh isoforms illustrate that subfamilies encode specificity in distinct ways through diversification loop region composition EC2...
Clustered protocadherins, a large family of paralogous proteins that play important roles in neuronal development, provide an case study interaction specificity eukaryotic protein family. A mammalian genome has more than 50 clustered protocadherin isoforms, which have remarkable homophilic for interactions between cellular surfaces. antiparallel dimer interface formed by the first 4 extracellular cadherin (EC) domains controls this interaction. To understand how is achieved numerous...
Abstract As the adoption and scope of genetic testing continue to expand, interpreting clinical significance DNA sequence variants at scale remains a formidable challenge, with high proportion classified as uncertain (VUSs). Genetic laboratories have historically relied, in part, on functional data from academic literature support variant classification. High-throughput assays or multiplex effect (MAVEs), designed assess effects protein stability function, represent an important increasingly...
G-quadruplexes are non-canonical DNA structures formed by guanine-rich sequences that implicated in cancer and aging. Understanding how small molecule ligands interact with quadruplexes is essential both to the development of novel anticancer therapeutics design new quadruplex-selective probes needed for elucidation quadruplex biological functions. In this work, UV–visible, fluorescence, circular dichroism spectroscopies, fluorescence resonance energy transfer (FRET) melting assays, light...
The crystal structure of the G-rich human telomeric DNA Tel22 has been determined at 1.35 Å resolution in space group P 6. forms a non-canonical called G-quadruplex. and unit-cell parameters are comparable to those structures with PDB codes 6ip3 (1.40 resolution) 1kf1 (2.15 resolution). G-quadruplexes highly similar all structures. However, this displays clear density for polyethylene glycol two potassium ions, which located outside ion channel G-quadruplex play an important role stabilizing...
Abstract Nramp family transporters—expressed in organisms from bacteria to humans—enable uptake of essential divalent transition metals via an alternating-access mechanism that includes proton co-transport. We present high-resolution structures Deinococcus radiodurans (Dra)Nramp at complementary stages its transport cycle provide a thorough description the by identifying key intramolecular rearrangements and changes metal coordination sphere. Strikingly, while requires cycling outward-to...
We present a novel approach for embedding experimental contact information in the protein structure prediction tool AlphaFold2 that harnesses principles of sequence coevolution to enforce disulfide connectivity patterns disulfide-rich peptide (DRP) structures. While generates accurate DRP most cases, it sometimes fails at predicting specific pattern multiple bonds. Here, we take advantage engineer alignment (MSA) input with by mutating highly conserved cysteines subsets MSA—which term...
ABSTRACT Protocadherins (Pcdhs) are cell adhesion and signaling proteins used by neurons to develop maintain neuronal networks, relying on trans homophilic interactions between their extracellular cadherin (EC) repeat domains. We present the structure of antiparallel EC1-4 homodimer human PcdhYB3, a member γ subfamily clustered Pcdhs. Structure sequence comparisons α, β, Pcdh isoforms illustrate that subfamilies encode specificity in distinct ways through diversification loop region...