A5074933688- ATP Synthase and ATPases Research
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Biochemical and Molecular Research
- Drug Transport and Resistance Mechanisms
- Lipid Membrane Structure and Behavior
- RNA and protein synthesis mechanisms
- Enzyme function and inhibition
- Photosynthetic Processes and Mechanisms
- Receptor Mechanisms and Signaling
- Bacteriophages and microbial interactions
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Monoclonal and Polyclonal Antibodies Research
- Amino Acid Enzymes and Metabolism
- Metalloenzymes and iron-sulfur proteins
- Enzyme Production and Characterization
- Enzyme Catalysis and Immobilization
- Complement system in diseases
- Escherichia coli research studies
- Erythrocyte Function and Pathophysiology
- Alkaline Phosphatase Research Studies
- Bacterial Genetics and Biotechnology
- Porphyrin Metabolism and Disorders
- Glycosylation and Glycoproteins Research
University of Helsinki
2015-2024
University of Leeds
2015-2024
Institute of Structural and Molecular Biology
2014-2024
Nankai University
2015-2020
National Tsing Hua University
2017
Czech Academy of Sciences, Institute of Biotechnology
2005-2013
Helsinki Institute of Physics
2001-2013
Toyama Prefectural University
2012
Flinders University
2012
Biocenter Finland
2003-2010
The three-dimensional structure of acetylcholinesterase from Torpedo californica electric organ has been determined by x-ray analysis to 2.8 angstrom resolution. form crystallized is the glycolipid-anchored homodimer that was purified subsequent solubilization with a bacterial phosphatidylinositol-specific phospholipase C. enzyme monomer an α/β protein contains 537 amino acids. It consists 12-stranded mixed β sheet surrounded 14 α helices and bears striking resemblance several hydrolase...
We have identified a new protein fold—the α/β hydrolase fold—that is common to several hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core each enzyme similar: an sheet, not barrel, eight β-sheets connected by α-helices. These diverged from ancestor so as preserve the arrangement residues, binding site. They all triad, elements which are borne on loops best-conserved structural features in fold. Only histidine nucleophile-histidine-acid triad...
The alternative pathway of complement is important in innate immunity, attacking not only microbes but all unprotected biological surfaces through powerful amplification. It unresolved how host and nonhost are distinguished at the molecular level, key components domains 19–20 regulator factor H (FH), which interact with (i.e., nonactivator surface glycosaminoglycans or sialic acids) C3d part C3b. Our structure FH19–20:C3d complex 2.3-Å resolution shows that FH19–20 has two distinct binding...
Vascular endothelial growth factors (VEGFs) regulate blood and lymph vessel formation through activation of three receptor tyrosine kinases, VEGFR-1, -2, -3. The extracellular domain VEGF receptors consists seven immunoglobulin homology domains, which, upon ligand binding, promote dimerization. Dimerization initiates transmembrane signaling, which activates the intracellular kinase receptor. VEGF-C stimulates lymphangiogenesis contributes to pathological angiogenesis via VEGFR-3. However,...
Actin dynamics provide the driving force for many cellular processes including motility and endocytosis. Among central cytoskeletal regulators are actin-depolymerizing factor (ADF)/cofilin, which depolymerizes actin filaments, twinfilin, sequesters monomers caps filament barbed ends. Both interact with through an ADF homology (ADF-H) domain, is also found in several other actin-binding proteins. However, absence of atomic structure ADF-H domain complex actin, mechanism by these proteins has...
Membrane-integral pyrophosphatases (M-PPases) are crucial for the survival of plants, bacteria, and protozoan parasites. They couple pyrophosphate hydrolysis or synthesis to Na(+) H(+) pumping. The 2.6-angstrom structure Thermotoga maritima M-PPase in resting state reveals a previously unknown solution ion hydrolytic center, 20 angstroms above membrane, is coupled gate formed by conserved Asp(243), Glu(246), Lys(707) an unusual "coupling funnel" six α helices. Comparison with our...
To cause infections microbes need to evade host defense systems, one of these being the evolutionarily old and important arm innate immunity, alternative pathway complement. It can attack all kinds targets is tightly controlled in plasma on cells by complement regulator factor H (FH). FH binds simultaneously cell surface structures such as heparin or glycosaminoglycans via domain 20 main opsonin C3b 19. Many pathogenic protect themselves from recruiting FH. We analyzed how why different bind...
The field of membrane protein structural biology has been revolutionized over the last few years with a number high profile structures being solved using cryo-EM including Piezo, Ryanodine receptor, TRPV1 and Glutamate receptor. Further developments in EM hold promise even greater progress terms resolution, which for proteins is still typically within 4–7 Å range. One advantage approach ability to study more "native" like environments example proteoliposomes, amphipols nanodiscs. Recently,...
We have solved the structures of mammalian mesencephalic astrocyte-derived neurotrophic factor (MANF) and conserved dopamine (CDNF). CDNF protects repairs midbrain dopaminergic neurons in vivo; MANF supports their survival culture is also cytoprotective against endoplasmic reticulum (ER) stress. Neither protein structure resembles any known growth but N-terminal domain a saposin-like lipid-binding domain. may thus bind lipids or membranes. Consistent with this, there are two patches lysines...
The crystal structure of the catalytic domain site-specific recombination enzyme gamma delta resolvase has been determined at 2.7 A resolution. Its first 120 amino acids form a central five-stranded, beta-pleated sheet surrounded by five alpha helices. In one four dyad-related dimers, two active site Ser-10 residues are 19 apart, perhaps close enough to contact and become covalently linked DNA site. This dimer also forms only closely packed tetramer found in crystal. subunit interface second...
Soluble inorganic pyrophosphatase (PPase), an essential enzyme central to phosphorus metabolism, catalyzes the hydrolysis of phosphoanhydride bond in pyrophosphate. Catalysis requires divalent metal ions which affect apparent pKas general acid and base on enzyme, pKa substrate. Three five are required for maximal activity, depending pH source. A detailed understanding catalysis would aid both nature biological mechanisms phosphoryl transfer, role cations. Without a high-resolution complex...
Glial cell line-derived neurotrophic factor (GDNF), a neuronal survival factor, binds its co-receptor GDNF family receptor α1 (GFRα1) in 2:2 ratio and signals through the tyrosine kinase RET. We have solved GDNF2·GFRα12 complex structure at 2.35 Å resolution presence of heparin mimic, sucrose octasulfate. The our previously published artemin2·GFRα32 are unlike three ways. First, we experimentally identified residues that differ ligand-GFRα interface between two structures, particular ones...