A5024943442- Protein Kinase Regulation and GTPase Signaling
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Microtubule and mitosis dynamics
- Cellular transport and secretion
- Melanoma and MAPK Pathways
- Cellular Mechanics and Interactions
- RNA and protein synthesis mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Cell death mechanisms and regulation
- Receptor Mechanisms and Signaling
- Endoplasmic Reticulum Stress and Disease
- Monoclonal and Polyclonal Antibodies Research
- Alzheimer's disease research and treatments
- Trypanosoma species research and implications
- Supramolecular Self-Assembly in Materials
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Chemical Synthesis and Analysis
- Glycosylation and Glycoproteins Research
- Research on Leishmaniasis Studies
- Cancer-related Molecular Pathways
- Photoreceptor and optogenetics research
- Molecular spectroscopy and chirality
- Mitochondrial Function and Pathology
University of Cambridge
2015-2025
Building Bridges
2016
Institut Curie
2009
Inserm
2009
Lawn Tennis Association
2007
GlaxoSmithKline (United Kingdom)
2005
UNC Lineberger Comprehensive Cancer Center
1996-1997
University of North Carolina at Chapel Hill
1996-1997
Oxford Research Group
1997
University of Oxford
1992-1996
Protein molecules have the ability to form a rich variety of natural and artificial structures materials. We show that amyloid fibrils, ordered supramolecular nanostructures are self-assembled from wide range polypeptide molecules, rigidities varying over four orders magnitude, constitute class high-performance biomaterials. elucidate molecular origin fibril material properties major contribution their rigidity stems generic interbackbone hydrogen-bonding network is modulated by variable...
The cross-β amyloid form of peptides and proteins represents an archetypal widely accessible structure consisting ordered arrays β-sheet filaments. These complex aggregates have remarkable chemical physical properties, the conversion normally soluble functional forms into structures is linked to many debilitating human diseases, including several common age-related dementia. Despite their importance, however, fibrils proved be recalcitrant detailed structural analysis. By combining...
The Raf-1 protein kinase is the best-characterized downstream effector of activated Ras. Interaction with Ras leads to activation and results in transduction cell growth differentiation signals. details are unclear, but our characterization a second Ras-binding site cysteine-rich domain (CRD) involvement both sites effective Raf-1-mediated transformation provides insight into molecular aspects consequences Ras-Raf interactions. CRD member an emerging family domains, many which found within...
Several species of African trypanosomes cause fatal disease in livestock, but most cannot infect humans due to innate trypanosome lytic factors (TLFs). Human TLFs are pore forming high-density lipoprotein (HDL) particles that contain apolipoprotein L-I (apoL-I) the trypanolytic component, and haptoglobin-related protein (Hpr), which binds free hemoglobin (Hb) blood facilitates uptake TLF via a haptoglobin-hemoglobin receptor. The human-infective Trypanosoma brucei rhodesiense escapes lysis...
Ras proteins cycle between active, guanosine triphosphate (GTP)-bound and inactive, diphospate (GDP)-bound states to mediate signal transduction pathways that promote cell growth differentiation. It is believed the major physiological mechanism for activation via interaction with guanine-nucleotide exchange factors (GEFs). This highly regulated results in elevated levels of Ras-GTP by facilitating GDP dissociation. Recently, a novel has been proposed, whereby nitric oxide (NO) modification...
IQGAP1 contains a domain related to the catalytic portion of GTPase-activating proteins (GAPs) for Ras small G proteins, yet it has no RasGAP activity and binds Rho family Cdc42 Rac1. It is thought that an effector Rac1 Cdc42, regulating cell-cell adhesion through E-cadherin-catenin complex, which controls formation maintenance adherens junctions. This study investigates binding interfaces Rac1-IQGAP1 Cdc42-IQGAP1 complexes. We mutated measured effects mutations on their affinity IQGAP1....
Abstract Background In a mammalian host, the cell surface of African trypanosomes is protected by monolayer single variant glycoprotein (VSG). The VSG central to antigenic variation; one gene expressed at any time and there low frequency stochastic switch expression different gene. genome Trypanosoma brucei contains repertoire > 1000 sequences. degree conservation genomic in strains has not been investigated detail. Results Eighteen VSGs from Ugandan isolates were compared with homologues...
Obtaining enough experimental restraints can be a limiting factor in the NMR structure determination of larger proteins. This is particularly case for large assemblies such as membrane proteins that have been solubilized membrane-mimicking environment. Whilst cases extensive deuteration strategies are regularly utilised with aim to improve spectral quality, these schemes often limit number NOEs obtainable, making complementary highly beneficial successful elucidation. Recently,...
Transducer of Cdc42-dependent actin assembly protein 1 (TOCA1) is an effector the Rho family small G Cdc42. It contains a membrane-deforming F-BAR domain as well Src homology 3 (SH3) and protein-binding region (HR1) domain. TOCA1 binding to Cdc42 leads rearrangements, which are thought be involved in processes such endocytosis, filopodia formation, cell migration. We have solved structure HR1 TOCA1, providing first structural data for this protein. found that HR1, like closely related CIP4...
Cdc42 is a member of the Rho family small G proteins. Signal transduction events emanating from lead to cytoskeletal rearrangements, cell proliferation, and differentiation. Many effector proteins have been identified for Cdc42; however, it not clear how certain effectors specifically recognize bind Cdc42, as opposed Rac or Rho, in many cases, which controls what cellular events. Mutations were introduced into at residues: Met1, Val8, Phe28, Tyr32, Val33, Thr35, Val36, Phe37, Asp38, Tyr40,...