A5086345439- Lipid Membrane Structure and Behavior
- Protein Structure and Dynamics
- ATP Synthase and ATPases Research
- Enzyme Structure and Function
- Photosynthetic Processes and Mechanisms
- RNA and protein synthesis mechanisms
- Amino Acid Enzymes and Metabolism
- Drug Transport and Resistance Mechanisms
- Receptor Mechanisms and Signaling
- Photoreceptor and optogenetics research
- Glycosylation and Glycoproteins Research
- Bacterial Genetics and Biotechnology
- Ion Transport and Channel Regulation
- Cellular transport and secretion
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Protein Kinase Regulation and GTPase Signaling
- Advanced Chemical Physics Studies
- Mass Spectrometry Techniques and Applications
- Atomic and Molecular Physics
- Chemical Synthesis and Analysis
- Parkinson's Disease Mechanisms and Treatments
- Polyamine Metabolism and Applications
- Complement system in diseases
- Adenosine and Purinergic Signaling
Aarhus University
2014-2024
Research Network (United States)
2023
European Bioinformatics Institute
2022
Danish Diabetes Academy
2022
Danish National Research Foundation
2015
Trinity College Dublin
2011-2015
University of Limerick
2009-2014
Mater Health Services
1994
Proton-coupled oligopeptide transporters belong to the major facilitator superfamily (MFS) of membrane transporters. Recent crystal structures suggest MFS fold facilitates transport through rearrangement their two six-helix bundles around a central ligand binding site; how this is achieved, however, poorly understood. Using modeling, molecular dynamics, crystallography, functional assays, and site-directed spin labeling combined with double electron-electron resonance (DEER) spectroscopy, we...
Scientific Report10 June 2014Open Access Structural basis for polyspecificity in the POT family of proton-coupled oligopeptide transporters Joseph A Lyons Schools Medicine and Biochemistry & Immunology, Trinity College Dublin, Ireland Search more papers by this author Joanne L Parker Department Biochemistry, University Oxford, UK Nicolae Solcan Alette Brinth Dianfan Li Syed TA Shah Martin Caffrey Corresponding Author Simon Newstead Information Lyons1,3,‡, Parker2,‡, Solcan2, Brinth1, Li1,...
X-ray crystallography reveals how a calixarene can bind to dimethyllysine form complex with features similar the aromatic cage motif of chromodomain bound histone tail.
P4-ATPases flip lipids from the exoplasmic to cytosolic leaflet, thus maintaining lipid asymmetry in eukaryotic cell membranes. Mutations several human P4-ATPase genes are associated with severe diseases, for example ATP8B1 causing progressive familial intrahepatic cholestasis, a rare inherited disorder progressing toward liver failure. forms binary complex CDC50A and displays broad specificity glycerophospholipids, but regulatory mechanisms unknown. Here, we report functional studies...
P4-ATPases define a eukaryotic subfamily of the P-type ATPases, and are responsible for transverse flip specific lipids from extracellular or luminal leaflet to cytosolic cell membranes. The enzymatic cycle ATPases is divided into autophosphorylation dephosphorylation half-reactions. Unlike most other transport their substrate during only, i.e. phosphorylation half-reaction not associated with transport. To study structural basis distinct mechanisms P4-ATPases, we have determined cryo-EM...
Abstract The sodium–potassium–chloride transporter NKCC1 of the SLC12 family performs Na + ‐dependent Cl − ‐ and K ‐ion uptake across plasma membranes. is important for regulating cell volume, hearing, blood pressure, regulation hyperpolarizing GABAergic glycinergic signaling in central nervous system. Here, we present a 2.6 Å resolution cryo‐electron microscopy structure human substrate‐loaded (Na , 2 ) occluded, inward‐facing state that has also been observed SLC6‐type transporters MhsT...
Asymmetric distribution of phospholipids in eukaryotic membranes is essential for cell integrity, signaling pathways, and vesicular trafficking. P4-ATPases, also known as flippases, participate creating maintaining this asymmetry through active transport from the exoplasmic to cytosolic leaflet. Here, we present a total nine cryo-electron microscopy structures human flippase ATP8B1-CDC50A complex at 2.4 3.1 Å overall resolution, along with functional computational studies, addressing...
Abstract Diacylglycerol kinase catalyses the ATP-dependent conversion of diacylglycerol to phosphatidic acid in plasma membrane Escherichia coli . The small size this integral trimer, which has 121 residues per subunit, means that available protein must be used economically craft three catalytic and substrate-binding sites centred about membrane/cytosol interface. How nature accomplished extraordinary feat is revealed here a crystal structure captured as ternary complex with bound lipid...
A simple and inexpensive protocol for producing crystals in the sticky viscous mesophase used membrane protein crystallization by meso method is described. It provides that appear within 15–30 min of setup at 293 K. The gives experimenter a convenient way gaining familiarity level comfort with lipidic cubic mesophase, which can be daunting as material when first encountered. Having to produce test protein, lysozyme, proceed confidence apply more valuable (and soluble) targets. glass sandwich...
P4-ATPases, also known as phospholipid flippases, are responsible for creating and maintaining transbilayer lipid asymmetry in eukaryotic cell membranes. Here, we use limited proteolysis to investigate the role of N C termini ATP hydrolysis auto-inhibition yeast flippase Drs2p-Cdc50p. We show that detergent-solubilized purified may result more than 1 order magnitude increase its ATPase activity, which remains dependent on phosphatidylinositol 4-phosphate (PI4P), a regulator this flippase,...
Gramicidin is an apolar pentadecapeptide antibiotic consisting of alternating d- and l-amino acids. It functions, in part, by creating pores membranes susceptible cells rendering them leaky to monovalent cations. The peptide should be able traverse the host membrane either as a double-stranded, intertwined double helix (DSDH) or head-to-head single-stranded (HHSH). Current structure models are based on macromolecular X-ray crystallography (MX) nuclear magnetic resonance (NMR). However, HHSH...