A5003886572- Protein Structure and Dynamics
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Microtubule and mitosis dynamics
- Genomics and Phylogenetic Studies
- Machine Learning in Bioinformatics
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Photosynthetic Processes and Mechanisms
- RNA regulation and disease
- Endoplasmic Reticulum Stress and Disease
- Genetic and Kidney Cyst Diseases
- Glycosylation and Glycoproteins Research
- Advanced Proteomics Techniques and Applications
- Protist diversity and phylogeny
- Genetics, Aging, and Longevity in Model Organisms
- Biochemical and Molecular Research
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- Analytical Chemistry and Chromatography
- Bacterial Genetics and Biotechnology
- Protein Kinase Regulation and GTPase Signaling
- Digital Imaging for Blood Diseases
MRC Laboratory of Molecular Biology
2014-2025
European Bioinformatics Institute
2012-2025
Medical Research Council
2005-2025
Wellcome Trust
2024-2025
University College London
2012
University of Bristol
2012
University of Cambridge
2012
Institute of Structural and Molecular Biology
2012
Hutchison/MRC Research Centre
2008-2009
Xi’an Jiaotong-Liverpool University
2009
The Structural Classification of Proteins (SCOP) database is a comprehensive ordering all proteins known structure, according to their evolutionary and structural relationships. SCOP hierarchy comprises the following levels: Species, Protein, Family, Superfamily, Fold Class. While keeping original classification scheme intact, we have changed production in order cope with rapid growth new data facilitate discovery protein We describe ongoing developments features implemented SCOP. A update...
The Structural Classification of Proteins (SCOP) database is a comprehensive ordering all proteins known structure, according to their evolutionary and structural relationships. Protein domains in SCOP are hierarchically classified into families, superfamilies, folds classes. continual accumulation sequence data allows more rigorous analysis provides important information for understanding the protein world its repertoire. participates project that aims rationalize integrate on held several...
Abstract The Structural Classification of Proteins (SCOP) database is a classification protein domains organised according to their evolutionary and structural relationships. We report major effort increase the coverage data, aiming provide almost all domain superfamilies with representatives in PDB. have also improved schema, provided new API modernised web interface. This by far most significant update since SCOP 1.75 builds on advances schema from 2 prototype. accessible...
We present a prototype of new structural classification proteins, SCOP2 (http://scop2.mrc-lmb.cam.ac.uk/), that we have developed recently. is successor to the Structural Classification Proteins (SCOP, http://scop.mrc-lmb.cam.ac.uk/scop/) database. Similarly SCOP, main focus organize structurally characterized proteins according their and evolutionary relationships. was designed provide more advanced framework for protein structure annotation classification. It defines approach essentially...
Self-assembly of a centriolar protein may contribute to organizing the cartwheel-like hub and establishing centriole symmetry.
We are now entering a new era in protein sequence and structure annotation, with hundreds of millions predicted structures made available through the AlphaFold database1. These models cover nearly all proteins that known, including those challenging to annotate for function or putative biological role using standard homology-based approaches. In this study, we examine extent which database has structurally illuminated 'dark matter' natural universe at high accuracy. further describe...
Abstract InterPro (https://www.ebi.ac.uk/interpro) is a freely accessible resource for the classification of protein sequences into families. It integrates predictive models, known as signatures, from multiple member databases to classify families and predict presence domains significant sites. The database provides annotations over 200 million sequences, ensuring extensive coverage UniProtKB, standard repository includes mappings several other major resources, such Gene Ontology (GO),...
Abstract Obtaining the high-resolution structures of proteins and their complexes is a crucial aspect understanding mechanisms life. Experimental structure determination methods are time-consuming, expensive cannot keep pace with growing number protein sequences available through genomic DNA sequencing. Thus, ability to accurately predict from sequence holy grail structural computational biology that would remove bottleneck in our efforts understand as well rationally engineer living...
Abstract Phosphorylation of the translation initiation factor eIF2α to initiate integrated stress response (ISR) is a vital signalling event. Protein kinases activating ISR, including PERK and GCN2, have attracted considerable attention for drug development. Here we find that widely used ATP-competitive inhibitors PERK, GSK2656157, GSK2606414 AMG44, inhibit in nanomolar range, but surprisingly activate ISR via GCN2 at micromolar concentrations. Similarly, PKR inhibitor, C16, also activates...
Abstract The Pfam protein families database is a comprehensive collection of domains and used for genome annotation structure function analysis (https://www.ebi.ac.uk/interpro/). This update describes major developments in since 2020, including decommissioning the website integration with InterPro, harmonization ECOD structural classification, expanded curation metagenomic, microprotein repeat-containing families. We highlight how AlphaFold predictions are being leveraged to refine domain...
Abstract The evolutionary classification of protein domains (ECOD) classifies using a combination sequence and structural data (http://prodata.swmed.edu/ecod). Here we present the culmination our previous efforts at classifying from predicted structures, principally AlphaFold Database (AFDB), by integrating these with existing PDB structures. This combined includes both previous, purely experimental, as well provisional 48 proteomes in AFDB model organisms concern to global health. ECOD over...
Human mitochondrial transcription factor A (TFAM) is a multi-functional protein, involved in different aspects of maintaining genome integrity. In this report, we characterized TFAM and its interaction with tumor suppressor p53 using various biophysical methods. DNA-free thermally unstable protein that equilibrium between monomers dimers. Self-association modulated by basic C-terminal tail. The DNA-binding ability mainly contributed first HMG-box, while the second HMG-box has low-DNA-binding...
Centrioles organise centrosomes and template cilia flagella. Several centriole centrosome proteins have been linked to microcephaly (MCPH), a neuro-developmental disease associated with small brain size. CPAP (MCPH6) STIL (MCPH7) are required for assembly, but it is unclear how mutations in them lead microcephaly. We show that the TCP domain of constitutes novel proline recognition forms 1:1 complex short, highly conserved target motif STIL. Crystal structures this reveal an unusual, all-β...
During their final maturation in the cytoplasm, pre-60S ribosomal particles are converted to translation-competent large subunits. Here, we present mechanism of peptidyltransferase centre (PTC) completion that explains how integration last proteins is coupled release nuclear export adaptor Nmd3. Single-particle cryo-EM reveals eL40 recruitment stabilises helix 89 form uL16 binding site. The loading unhooks 38 from Nmd3 adopt its mature conformation. In turn, partial retraction L1 stalk a...
The tumor suppressor p53 consists of four 393-residue chains, each which has two natively unfolded (N- and C-terminal) folded (core tetramerization) domains. Their structural organization is poorly characterized as the protein tends to aggregate, defied crystallization, at limits NMR studies. We first stabilized by mutation make it more suitable for extended study then acquired spectra on full-length various combinations shorter domain constructs. spectrum ( 15 N, 1 H transverse relaxation...
Genome3D, available at http://www.genome3d.eu, is a new collaborative project that integrates UK-based structural resources to provide unique perspective on sequence–structure–function relationships. Leading structure prediction (DomSerf, FUGUE, Gene3D, pDomTHREADER, Phyre and SUPERFAMILY) annotations for UniProt sequences indicate the locations of domains (structural annotations) their 3D structures models). Structural model predictions are currently three genomes (Homo sapiens, E. coli...
Genome3D (http://www.genome3d.eu) is a collaborative resource that provides predicted domain annotations and structural models for key sequences. Since introducing in previous NAR paper, we have substantially extended improved the resource. We annotated representatives from Pfam families to improve coverage of diverse sequences added fast sequence search website allow users find Genome3D-annotated similar their own. data, enlarging source data set three model organisms 10, adding VIVACE, new...
With the increasing amount of structural data, number homologous protein structures bearing topological irregularities is steadily growing. These include proteins with circular permutations, segment-swapping, context-dependent folding or chameleon sequences that can adopt alternative secondary structures. Their non-trivial relationships are readily identified during expert analysis but their automatic identification using existing computational tools still remains difficult impossible. Such...
p53 maintains genome integrity either by regulating the transcription of genes involved in cell cycle, apoptosis, and DNA repair or interacting with partner proteins. Here we provide evidence for a direct physical interaction between tumor suppressors BRCA2. We found that transactivation domain made specific interactions C-terminal oligonucleotide/oligosaccharide-binding-fold domains BRCA2 (BRCA2 CTD ). A second distinct site situated on DNA-binding domain, bound to region containing BRC...
Centrosomes are required for faithful chromosome segregation during mitosis. They composed of a centriole pair that recruits and organizes the microtubule-nucleating pericentriolar material. Centriole duplication is tightly controlled in vivo aberrations this process associated with several human diseases, including cancer microcephaly. Although factors essential assembly, such as STIL PLK4, have been identified, underlying molecular mechanisms drive incompletely understood. Combining...
Cilia are thin cell projections with essential roles in motility, fluid movement, sensing, and signaling. They templated from centrioles that dock against the plasma membrane subsequently extend their peripheral microtubule array. The molecular mechanisms underpinning cilia assembly incompletely understood. Cep104 is a key factor involved formation length regulation rides on ends of elongating shrinking cilia. It mutated Joubert syndrome, genetically heterogeneous ciliopathy. Here we provide...