A5086689325- Cell death mechanisms and regulation
- RNA Interference and Gene Delivery
- Protein Structure and Dynamics
- Mitochondrial Function and Pathology
- Computational Drug Discovery Methods
- Poxvirus research and outbreaks
- Ubiquitin and proteasome pathways
- Virus-based gene therapy research
- Asymmetric Synthesis and Catalysis
- ATP Synthase and ATPases Research
- Chemical Synthesis and Analysis
- Enzyme Structure and Function
- Alzheimer's disease research and treatments
- Cancer-related Molecular Pathways
- Trace Elements in Health
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Synthetic Organic Chemistry Methods
- Photosynthetic Processes and Mechanisms
- Cancer Treatment and Pharmacology
- interferon and immune responses
- Hemoglobin structure and function
- DNA and Nucleic Acid Chemistry
- Marine Invertebrate Physiology and Ecology
- Supramolecular Self-Assembly in Materials
University of Birmingham
2024
The University of Melbourne
2012-2024
La Trobe University
2015-2023
Queen's University
2023
Severn Trent (United Kingdom)
2017
Walter and Eliza Hall Institute of Medical Research
2004-2013
Milbank Memorial Fund
2011-2012
Centenary Institute
2009
The Royal Melbourne Hospital
1997-2003
Human Factors (Norway)
1999
Apoptosis is held in check by prosurvival proteins of the Bcl-2 family. The distantly related BH3-only bind to and antagonize them, thereby promoting apoptosis. Whereas binding protein Noxa Mcl-1 induces degradation proteasome, another ligand, Bim, elevates levels. We compared three-dimensional structures complexes formed between BH3 peptides both Bim Noxa, we show that a discrete C-terminal sequence necessary instigate degradation.
A major source of free radical production in the brain derives from copper. To prevent metal-mediated oxidative stress, cells have evolved complex metal transport systems. The Alzheimer's disease amyloid precursor protein (APP) is a regulator neuronal copper homeostasis. APP knockout mice elevated levels cerebral cortex, whereas APP-overexpressing transgenic reduced levels. Importantly, binding to can greatly reduce औ vitro. understand this interaction at molecular level we solved structure...
The B cell lymphoma-2 (Bcl-2) homologs myeloid leukemia-1 (Mcl-1) and A1 are prosurvival factors that selectively bind a subset of proapoptotic Bcl homology (BH) 3-only proteins. To investigate the molecular basis selectivity, we determined solution structure C-terminal Bcl-2-like domain Mcl-1. This shares features expected Bcl-2 protein, having helical fold centered on core hydrophobic helix surface-exposed groove for binding its cognate partners. A number residues in differentiate Mcl-1...
The mitochondrial pathway of apoptosis is initiated by Bcl-2 homology region 3 (BH3)-only members the protein family. On upregulation or activation, certain BH3-only proteins can directly bind and activate Bak Bax to induce conformation change, oligomerization pore formation in mitochondria. proteins, with exception Bid, are intrinsically disordered therefore, functional studies often utilize peptides based on just their BH3 domains. However, these reagents do not possess hydrophobic...
Programmed cell death is a tightly controlled process critical for the removal of damaged or infected cells. Pro- and antiapoptotic proteins Bcl-2 family are pivotal mediators this process. African swine fever virus (ASFV) large DNA virus, only member Asfarviridae family, harbors A179L, putative like protein. A179L has been shown to bind several proapoptotic proteins; however, hierarchy binding structural basis apoptosis inhibition currently not understood. We systematically evaluated...
The extracellular accumulation of amyloid β (Aβ) peptides is characteristic Alzheimer's disease (AD). However, formation diffusible, oligomeric forms Aβ, both on and off pathways to fibrils, thought include neurotoxic species responsible for synaptic loss neurodegeneration, rather than polymeric aggregates. 8-hydroxyquinolines (8-HQ) clioquinol (CQ) PBT2 were developed their ability inhibit metal-mediated generation reactive oxygen from Aβ:Cu complexes have undergone preclinical Phase II...
In metazoans, Bcl-2 family proteins are major regulators of mitochondrially mediated apoptosis; however, their evolution remains poorly understood. Here, we describe the molecular characterization four members in most primitive metazoan, Trichoplax adhaerens All trBcl-2 homologs multimotif group, with trBcl-2L1 and trBcl-2L2 being highly divergent antiapoptotic members, whereas trBcl-2L3 trBcl-2L4 proapoptotic Bax Bak, respectively. trBax expression permeabilizes mitochondrial outer...
Prosurvival Bcl-2–like proteins, like Bcl-w, are thought to function on organelles such as the mitochondrion and be targeted them by their hydrophobic COOH-terminal domain. We unexpectedly found, however, that membrane association of Bcl-w was enhanced during apoptosis. In healthy cells, loosely attached mitochondrial membrane, but it converted into an integral protein cytotoxic signals induce binding BH3-only Bim, or addition BH3 peptides lysates. As structure has revealed its domain...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis, conformational properties, and antibody recognition of peptides containing .beta.-turn mimetics based on .alpha.-alkylproline derivativesMark G. Hinds, John H. Welsh, David M. Brennand, J. Fisher, Martin Glennie, Nigel Richards, L. Turner, A. RobinsonCite this: Med. Chem. 1991, 34, 6, 1777–1789Publication Date (Print):June 1, 1991Publication History Published online1 May 2002Published inissue 1 June...