Structural basis of substrate specificity of human oligosaccharyl transferase subunit N33/Tusc3 and its role in regulating protein N-glycosylation.

N-linked glycosylation of proteins in the endoplasmic reticulum (ER) is essential in eukaryotes and catalyzed by oligosaccharyl transferase (OST). Human OST is a hetero-oligomer of seven subunits. The subunit N33/Tusc3 is a tumor suppressor candidate, and defects in the subunit N33/Tusc3 are linked with nonsyndromic mental retardation.

Mechanism of the prokaryotic transmembrane disulfide reduction pathway and its in vitro reconstitution from purified components.

Making your (Dsb) connection: the redox pathway bringing reducing equivalents from bacterial cytoplasm, across the inner membrane, to the three reductive Dsb pathways in the otherwise oxidizing periplasm (see scheme; TR=thioredoxin reductase, Trx=thioredoxin) is reconstituted from purified components. Transfer of reducing equivalents across the membrane is demonstrated and underlying mechanistic details are revealed.

Thermodynamic and structural description of allosterically regulated VEGFR-2 dimerization.

VEGFs activate 3 receptor tyrosine kinases, VEGFR-1, VEGFR-2, and VEGFR-3, promoting angiogenic and lymphangiogenic signaling. The extracellular receptor domain (ECD) consists of 7 Ig-homology domains; domains 2 and 3 (D23) represent the ligand-binding domain, whereas the function of D4-7 is unclear. Ligand binding promotes receptor dimerization and instigates transmembrane signaling and receptor kinase activation.

Structural analysis of vascular endothelial growth factor receptor-2/ligand complexes by small-angle X-ray solution scattering.

Receptor tyrosine kinases play essential roles in tissue development and homeostasis, and aberrant signaling by these molecules is the basis of many diseases. Understanding the activation mechanism of these receptors is thus of high clinical relevance. We investigated vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs), which regulate blood and lymph vessel formation.

Oxidoreductase activity of oligosaccharyltransferase subunits Ost3p and Ost6p defines site-specific glycosylation efficiency.

Asparagine-linked glycosylation is a common posttranslational modification of diverse secretory and membrane proteins in eukaryotes, where it is catalyzed by the multiprotein complex oligosaccharyltransferase. The functions of the protein subunits of oligoasccharyltransferase, apart from the catalytic Stt3p, are ill defined. Here we describe functional and structural investigations of the Ost3/6p components of the yeast enzyme.

A structural and biochemical basis for PAPS-independent sulfuryl transfer by aryl sulfotransferase from uropathogenic Escherichia coli.

Sulfotransferases are a versatile class of enzymes involved in numerous physiological processes. In mammals, adenosine 3'-phosphate-5'-phosphosulfate (PAPS) is the universal sulfuryl donor, and PAPS-dependent sulfurylation of small molecules, including hormones, sugars, and antibiotics, is a critical step in hepatic detoxification and extracellular signaling. In contrast, little is known about sulfotransferases in bacteria, which make use of sulfurylated molecules as mediators of cell-cell interactions and host-pathogen interactions.

DsbL and DsbI form a specific dithiol oxidase system for periplasmic arylsulfate sulfotransferase in uropathogenic Escherichia coli.

Disulfide bond formation in the Escherichia coli periplasm requires the transfer of electrons from substrate proteins to DsbA, which is recycled as an oxidant by the membrane protein DsbB. The highly virulent, uropathogenic E. coli strain CFT073 contains a second, homologous pair of proteins, DsbL and DsbI, which are encoded in a tri-cistronic operon together with a periplasmic, uropathogen-specific arylsulfate sulfotransferase (ASST).