
Professor
Pharmaceutical Chemistry
+1 415 502-1897
We investigate molecular machines that coordinate gene expression or antiviral immunity. Research areas include : i- RNA decay enzymes that act in mRNA quality control and gene regulatory pathways, and ii- nucleic acid based immune systems that protect animals from viruses and neutralization of these systems by viral accessory proteins. We use tools from molecular biophysics to understand the structure and regulatory conformational dynamics in these systems with the ultimate goal of defining molecular mechanisms and avenues for structure based drug design.
Publications
APOBEC3G Antagonism by Vif, or When Structure Meets Biological and Evolutionary Studies.
Annual review of virology
CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis.
bioRxiv : the preprint server for biology
Structure of the E3 ligase CRL2-ZYG11B with substrates reveals the molecular basis for N-degron recognition and ubiquitination.
bioRxiv : the preprint server for biology
Enhanced NF-κB activation via HIV-1 Tat-TRAF6 cross-talk.
Science advances
A call to order: Examining structured domains in biomolecular condensates.
Journal of magnetic resonance (San Diego, Calif. : 1997)
Fluorescence-Based Activity Screening Assay Reveals Small Molecule Inhibitors of Vaccinia Virus mRNA Decapping Enzyme D9.
ACS chemical biology
Structure of the poxvirus decapping enzyme D9 reveals its mechanism of cap recognition and catalysis.
Structure (London, England : 1993)
SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein.
bioRxiv : the preprint server for biology
Biomolecular condensates amplify mRNA decapping by biasing enzyme conformation.
Nature chemical biology
Structural Insights into the Interaction of Clinically Relevant Phosphorothioate mRNA Cap Analogs with Translation Initiation Factor 4E Reveal Stabilization via Electrostatic Thio-Effect.
ACS chemical biology
Pat1 increases the range of decay factors and RNA bound by the Lsm1-7 complex.
RNA (New York, N.Y.)
Biophysical Properties of HP1-Mediated Heterochromatin.
Cold Spring Harbor symposia on quantitative biology
Structural Basis for a Species-Specific Determinant of an SIV Vif Protein toward Hominid APOBEC3G Antagonism.
Cell host & microbe
Pat1 activates late steps in mRNA decay by multiple mechanisms.
Proceedings of the National Academy of Sciences of the United States of America
ARIH2 Is a Vif-Dependent Regulator of CUL5-Mediated APOBEC3G Degradation in HIV Infection.
Cell host & microbe
Conformational Dynamics of the HIV-Vif Protein Complex.
Biophysical journal
Structural and molecular mechanisms for the control of eukaryotic 5'-3' mRNA decay.
Nature structural & molecular biology
Decapping enzymes STOP "cancer" ribosomes in their tracks.
The EMBO journal
A Viral Protein Restricts Drosophila RNAi Immunity by Regulating Argonaute Activity and Stability.
Cell host & microbe
CRL4AMBRA1 targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling.
The EMBO journal
Control of mRNA decapping by autoinhibition.
Nucleic acids research
Structure of the activated Edc1-Dcp1-Dcp2-Edc3 mRNA decapping complex with substrate analog poised for catalysis.
Nature communications
Fab-based inhibitors reveal ubiquitin independent functions for HIV Vif neutralization of APOBEC3 restriction factors.
PLoS pathogens
Making Sense of Multifunctional Proteins: Human Immunodeficiency Virus Type 1 Accessory and Regulatory Proteins and Connections to Transcription.
Annual review of virology
Biochemical Basis for Distinct Roles of the Heterochromatin Proteins Swi6 and Chp2.
Journal of molecular biology
Distortion of histone octamer core promotes nucleosome mobilization by a chromatin remodeler.
Science (New York, N.Y.)
CBFß and HIV Infection.
Advances in experimental medicine and biology
Structural basis of mRNA-cap recognition by Dcp1-Dcp2.
Nature structural & molecular biology
Two-headed tetraphosphate cap analogs are inhibitors of the Dcp1/2 RNA decapping complex.
RNA (New York, N.Y.)
A mutually assured destruction mechanism attenuates light signaling in Arabidopsis.
Science (New York, N.Y.)
Active site conformational dynamics are coupled to catalysis in the mRNA decapping enzyme Dcp2.
Structure (London, England : 1993)
The glucocorticoid receptor dimer interface allosterically transmits sequence-specific DNA signals.
Nature structural & molecular biology
Judge, jury, and executioner: DXO functions as a decapping enzyme and exoribonuclease in pre-mRNA quality control.
Molecular cell
From systems to structure: bridging networks and mechanism.
Molecular cell
CBFß stabilizes HIV Vif to counteract APOBEC3 at the expense of RUNX1 target gene expression.
Molecular cell
In support of the BMRB.
Nature structural & molecular biology
The crystal structure of the periplasmic domain of Vibrio parahaemolyticus CpxA.
Protein science : a publication of the Protein Society
Interdomain dynamics and coactivation of the mRNA decapping enzyme Dcp2 are mediated by a gatekeeper tryptophan.
Proceedings of the National Academy of Sciences of the United States of America
Dcp1 links coactivators of mRNA decapping to Dcp2 by proline recognition.
RNA (New York, N.Y.)
The crystal structure Escherichia coli Spy.
Protein science : a publication of the Protein Society
A split active site couples cap recognition by Dcp2 to activation.
Nature structural & molecular biology
Cricket paralysis virus antagonizes Argonaute 2 to modulate antiviral defense in Drosophila.
Nature structural & molecular biology
Identification and analysis of the interaction between Edc3 and Dcp2 in Saccharomyces cerevisiae.
Molecular and cellular biology
An extended structure of the APOBEC3G catalytic domain suggests a unique holoenzyme model.
Journal of molecular biology
Ligand-induced conformational heterogeneity of cytochrome P450 CYP119 identified by 2D NMR spectroscopy with the unnatural amino acid (13)C-p-methoxyphenylalanine.
Journal of the American Chemical Society
Decreased recognition of SUMO-sensitive target genes following modification of SF-1 (NR5A1).
Molecular and cellular biology
SRP RNA controls a conformational switch regulating the SRP-SRP receptor interaction.
Nature structural & molecular biology
A kinetic assay to monitor RNA decapping under single- turnover conditions.
Methods in enzymology
Backbone and sidechain methyl Ile (delta1), Leu and Val resonance assignments of the catalytic domain of the yeast mRNA decapping enzyme, Dcp2.
Biomolecular NMR assignments
Folding transitions during assembly of the eukaryotic mRNA cap-binding complex.
Journal of molecular biology
A methylation-dependent electrostatic switch controls DNA repair and transcriptional activation by E. coli ada.
Molecular cell
NMR structure of the flavin domain from soluble methane monooxygenase reductase from Methylococcus capsulatus (Bath).
Biochemistry
The mRNA cap-binding protein eIF4E in post-transcriptional gene expression.
Nature structural & molecular biology
Ribosome loading onto the mRNA cap is driven by conformational coupling between eIF4G and eIF4E.
Cell
Broadband 13C-13C adiabatic mixing in solution optimized for high fields.
Journal of magnetic resonance (San Diego, Calif. : 1997)
A sensitive and robust method for obtaining intermolecular NOEs between side chains in large protein complexes.
Journal of biomolecular NMR
A novel approach for characterizing protein ligand complexes: molecular basis for specificity of small-molecule Bcl-2 inhibitors.
Journal of the American Chemical Society
Global Fold Determination of large proteins using site-directed spin labeling
Protein NMR for the Millenium
Interactions of the eukaryotic translation initiation factor eIF4E.
Cold Spring Harbor symposia on quantitative biology
The Cap-binding protein eIF4E promotes folding of a functional domain of yeast translation initiation factor eIF4G1.
The Journal of biological chemistry
Determination of the peptide torsion angle phi by 15N chemical shift and 13Calpha-1Halpha dipolar tensor correlation in solid-state MAS NMR.
Journal of magnetic resonance (San Diego, Calif. : 1997)
Effects of membrane peptide dynamics on high-resolution magic-angle spinning NMR
Journal de Chimie Physique et de Physico-Chimie Biologique
Tilted n-fold symmetric radio frequency pulse sequences: Applications to CSA and heteronuclear dipolar recoupling in homonuclear dipolar coupled spin networks
The Journal of Chemical Physics
Coupling amplification in 2D MAS NMR and its application to torsion angle determination in peptides.
Journal of magnetic resonance (San Diego, Calif. : 1997)
Dipolar recoupling in MAS NMR: a probe for segmental order in lipid bilayers
Journal of the American Chemical Society
Site-Resolved Determination of Peptide Torsion Angle phi from the relative orientation of backbone NH and CH bonds by solid-state NMR
The Journal of Physical Chemistry B
Solid-state NMR measurement of psi in peptides: a NCCN 2Q-heteronuclear local field experiment
Chemical Physics Letters
Multidimensional NMR in lipid systems. Coherence transfer through J couplings under MAS
Journal of Magnetic Resonance Series B
Structural studies of a family of high affinity ligands for GPIIb/IIIa
Journal of the American Chemical Society