A5017617973- Enzyme Structure and Function
- Plant Molecular Biology Research
- Protein Structure and Dynamics
- Plant Reproductive Biology
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Photosynthetic Processes and Mechanisms
- Plant Gene Expression Analysis
- Advanced X-ray Imaging Techniques
- Advanced Electron Microscopy Techniques and Applications
- Particle Accelerators and Free-Electron Lasers
- Biochemical and Molecular Research
- Particle accelerators and beam dynamics
- Ubiquitin and proteasome pathways
- X-ray Spectroscopy and Fluorescence Analysis
- Ion channel regulation and function
- Inorganic Fluorides and Related Compounds
- Mosquito-borne diseases and control
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Crystallography and molecular interactions
- Genomics and Chromatin Dynamics
- Melanoma and MAPK Pathways
- Radiation Detection and Scintillator Technologies
- Phytochemical and Pharmacological Studies
European Synchrotron Radiation Facility
2011-2024
Genetic Alliance UK (United Kingdom)
2021
European Molecular Biology Laboratory
2006-2019
Unit of Virus Host Cell Interactions
2012-2019
Université Grenoble Alpes
2004-2019
Elkhorn Slough Foundation
2017
Exelixis (United States)
2006-2016
Centre National de la Recherche Scientifique
2003-2015
Université Joseph Fourier
2003-2014
Diamond Light Source
2011
Significance Auxin is a critical plant hormone that regulates every aspect of growth and development. AUXIN RESPONSE FACTOR (ARF) transcription factors control auxin-regulated gene transcription, their activity regulated by AUXIN/INDOLE 3-ACETIC ACID repressor proteins. This work identifies dimerization the with factor insufficient to repress activity, suggesting multimerization mechanism repressing ARF transcriptional further raising possibility in other systems may play roles repression.
Tank-binding kinase I (TBK1) plays a key role in the innate immune system by integrating signals from pattern-recognition receptors. Here, we report X-ray crystal structures of inhibitor-bound inactive and active TBK1 determined to 2.6 Å 4.0 resolution, respectively. The reveal compact dimer made up trimodular subunits containing an N-terminal domain (KD), ubiquitin-like (ULD), α-helical scaffold dimerization (SDD). Activation rearranges KD into conformation while maintaining overall...
The processes of genome replication and transcription SARS-CoV-2 represent important targets for viral inhibition. Betacoronaviral nucleoprotein (N) is a highly dynamic cofactor the replication-transcription complex (RTC), whose function depends on an essential interaction with amino-terminal ubiquitin-like domain nsp3 (Ubl1). Here, we describe this (dissociation constant - 30 to 200 nM) at atomic resolution. implicates two linear motifs in intrinsically disordered linker (N3), hydrophobic...
Dengue fever is an important emerging public health concern, with several million viral infections occurring annually, for which no effective therapy currently exists. The NS3 protein from virus a multifunctional of 69 kDa, endowed protease, helicase, and nucleoside 5'-triphosphatase (NTPase) activities. Thus, plays role in replication represents very interesting target the development specific antiviral inhibitors. We present structure enzymatically active fragment NTPase/helicase catalytic...
Abstract Motivation: Individual research groups now analyze thousands of samples per year at synchrotron macromolecular crystallography (MX) resources. The efficient management experimental data is thus essential if the best possible experiments are to be performed and used in downstream processes structure determination pipelines. Information System for Protein Beamlines (ISPyB), a Laboratory Management (LIMS) with an underlying model allowing integration analyses down-stream collection...
Acyl acid amido synthetases of the GH3 family act as critical prereceptor modulators plant hormone action; however, molecular basis for their selectivity is unclear. Here, we report crystal structures benzoate-specific Arabidopsis thaliana AtGH3.12/PBS3 and jasmonic acid-specific AtGH3.11/JAR1. These structures, combined with biochemical analysis, define features conjugation amino acids to diverse acyl substrates highlight importance conformational changes in carboxyl-terminal domain...
Transcription factors (TFs) are key players in evolution. Changes affecting their function can yield novel life forms but may also have deleterious effects. Consequently, gene duplication events that release one copy from selective pressure thought to be the common mechanism by which TFs acquire new activities. Here, we show LEAFY, a major regulator of flower development and cell division land plants, underwent changes its DNA binding specificity, even though plant genomes generally contain...
The development of automated high-intensity macromolecular crystallography (MX) beamlines at synchrotron facilities has resulted in a remarkable increase sample throughput. Developments X-ray detector technology now mean that complete diffraction datasets can be collected less than one minute. Such high-speed collection, and the volumes data it produces, often make difficult for even most experienced users to cope with deluge. However, careful reduction during experimental sessions is...
The Evening Complex (EC), composed of the DNA binding protein LUX ARRHYTHMO (LUX) and two additional proteins EARLY FLOWERING 3 (ELF3) ELF4, is a transcriptional repressor complex core component plant circadian clock. In addition to maintaining oscillations in clock gene expression, EC also participates temperature light entrainment, acting as an important environmental sensor conveying this information growth developmental pathways. However, molecular basis for specificity...
Abstract In plants, MADS domain transcription factors act as central regulators of diverse developmental pathways. Arabidopsis thaliana, one the most members this family is SEPALLATA3 (SEP3), which involved in many aspects plant reproduction, including floral meristem and organ development. SEP3 has been shown to form homo heterooligomeric complexes with other through its intervening (I) keratin-like (K) domains. function depends on ability specific protein-protein complexes; however, atomic...
Abstract Deciphering the mechanisms directing transcription factors (TFs) to specific genome regions is essential understand and predict transcriptional regulation. TFs recognize short DNA motifs primarily through their DNA-binding domain. Some also possess an oligomerization domain suspected potentiate binding but for which genome-wide influence remains poorly understood. Here we focus on LEAFY factor, a master regulator of flower development in angiosperms. We have determined crystal...
Transcriptional repression involves a class of proteins called corepressors that link transcription factors to chromatin remodeling complexes. In plants such as Arabidopsis thaliana, the most prominent corepressor is TOPLESS (TPL), which plays key role in hormone signaling and development. Here we present crystallographic structure TPL N-terminal region comprising LisH CTLH (C-terminal LisH) domains newly identified third region, corresponds CRA domain. Comparing with mammalian TBL1, shares...
Liquid-liquid phase separation (LLPS) is an important mechanism enabling the dynamic compartmentalization of macromolecules, including complex polymers such as proteins and nucleic acids, occurs a function physicochemical environment. In model plant,
We report the crystal structure of glycosylated ligand-binding (S1S2) domain kainate receptor subunit GluR6, in complex with agonist domoate. The shows expected overall homology AMPA and NMDA structures but reveals an unexpected binding mode for side chain domoate, which contact is made to larger lobe only (lobe I). In common GluR2, GluR6 S1S2 associates as a dimer, many interdimer contacts being conserved. Subtle differences these provide structural explanation why GluR2 L483Y GluR3 L507Y...
Significance In the mitogen-activated protein kinase (MAPK) pathways, N-terminal intrinsically disordered regulatory domains of MAPK kinases (MKK) control signaling specificity by binding to their cognate MAPKs via docking sites carrying homologous recognition sequences. MKK7 activates c-Jun (JNK) pathway and is only MKK containing three motifs within its domain. Here we obtain a comprehensive picture structure, dynamics, affinity, stoichiometry, kinetics MKK7–JNK complex. Importantly, show...
ARS2 is a highly conserved metazoan protein involved in numerous aspects of nuclear RNA metabolism. As direct partner the cap-binding complex (CBC), it mediates interactions with diverse processing and transport machineries transcript-dependent manner. Here, we present human crystal structure, which exhibits similarities metazoan-specific differences to plant homologue SERRATE, most notably an additional RRM domain. We biochemical, biophysical cellular interactome data comparing wild type...
Abstract The MADS transcription factors (TF) are an ancient eukaryotic protein family. In plants, the family is divided into two main lineages. Here, we demonstrate that DNA binding in both lineages absolutely requires a short amino acid sequence C-terminal to domain (M domain) called Intervening (I was previously defined only type II lineage MADS. Structural elucidation of MI domains from floral regulator, SEPALLATA3 (SEP3), shows conserved fold with I acting stabilise M domain. Using organ...
The ALOG (Arabidopsis LIGHT-DEPENDENT SHORT HYPOCOTYLS 1 (LSH1) and Oryza G1) proteins are conserved plant-specific Transcription Factors (TFs). They play critical roles in the development of various plant organs (meristems, inflorescences, floral organs, nodules) from bryophytes to higher flowering plants. Despite fact that first members this family were originally discovered Arabidopsis, their role model has remained poorly characterized. Moreover, how these transcriptional regulators work...
MXCuBE2 is the second-generation evolution of MXCuBE beamline control software, initially developed and used at ESRF – European Synchrotron. extends, in an intuitive graphical user interface (GUI), functionalities data collection methods available to users while keeping all previously features allowing for straightforward incorporation ongoing future developments. introduces extended abstraction layer that allows easy interfacing any kind macromolecular crystallography (MX) hardware...
ID23-2 is a fixed-energy (14.2 keV) microfocus beamline at the European Synchrotron Radiation Facility (ESRF) dedicated to macromolecular crystallography. The optics and sample environment have recently been redesigned rebuilt take full advantage of upgrade ESRF fourth generation Extremely Brilliant Source (ESRF-EBS). upgraded now makes use two sets compound refractive lenses multilayer mirrors obtain highly intense (>10 13 photons s −1 ) focused microbeam (minimum size 1.5 µm × 3 width...