Superantigen architecture: Functional decoration on a conserved scaffold

A defining and consistent feature of the bacterial superantigens from Staphylococcus aureus and Streptococcus pyogenes is their strongly conserved three-dimensional structure. Structural studies to date show that the array of more than 280 amino acid sequences known for superantigens (SAgs) and staphylococcal superantigen-like (SSL) proteins all have the same fold-a structure in which the same three-dimensional arrangement of α-helices and β-sheets is traced by each amino acid sequence, with the same topology (for recent reviews, see references 29 and 43). A typical SAg structure comprises two domains-an N-terminal β -barrel domain called an OB-fold (4, 25) and a C-terminal β-grasp domain in which a long α-helix packs on to a mixed parallel and antiparallel β-sheet. These two domains are traversed by an α-helix that lies at the N terminus of the protein and packs against the β-grasp domain, thus linking the N- and C-terminal domains

Role of the Hyaluronan Receptor, Stabilin-2/HARE, in Health and Disease

Stabilin-2/HARE is the primary clearance receptor for circulating hyaluronan (HA), a polysaccharide found in the extracellular matrix (ECM) of metazoans. HA has many biological functions including joint lubrication, ocular turgor pressure, skin elasticity and hydration, cell motility, and intercellular signaling, among many others. The regulatory system for HA content in the tissues, lymphatics, and circulatory systems is due, in part, to Stabilin-2/HARE. The activity of this receptor was discovered about 40 years ago (early 1980s), cloned in the mid-1990s, and has been characterized since then. Here, we discuss the overall domain organization of this receptor and how it correlates to ligand binding, cellular signaling, and its role in known physiological disorders such as cancer

Supersymmetric Open Wilson Lines

In this paper we study Open Wilson Lines (OWL's) in the context of two Supersymmetric Yang Mills theories. First we consider four dimensional N=2 Supersymmetric Yang Mills Theory with hypermultiplets transforming in the fundamental representation of the gauge group, and find supersymmetric OWL's only in the superconformal versions of these theories. We then consider four dimensional N=4 SYM coupled to a three dimensional defect hypermultiplet. Here there is a semi-circular supersymmetric OWL, which is related to the ray by a conformal transformation. We perform a perturbative calculation of the operators in both theories, and discuss using localization to compute them non-perturbatively.Comment: 26 pages, 3 figure

The structure of glucose-fructose oxidoreductase from Zymomonas mobilis: an osmoprotective periplasmic enzyme containing non-dissociable NADP

AbstractBackground The organism Zymomonas mobilis occurs naturally in sugar-rich environments. To protect the bacterium against osmotic shock, the periplasmic enzyme glucose-fructose oxidoreductase (GFOR) produces the compatible, solute sorbitol by reduction of fructose, coupled with the oxidation of glucose to gluconolactone. Hence, Z. mobilis can tolerate high concentrations of sugars and this property may be useful in the development of an efficient microbial process for ethanol production. Each enzyme subunit contains tightly associated NADP which is not released during the catalytic cycle.Results The structure of GFOR was determined by X-ray crystallography at 2.7 å resolution. Each subunit of the tetrameric enzyme comprises two domains, a classical dinucleotide-binding domain, and a C-terminal domain based on a predominantly antiparallel nine-stranded β sheet. In the tetramer, the subunits associate to form two extended 18-stranded β sheets, which pack against each other in a face to face fashion, creating an extensive interface at the core of the tetramer. An N-terminal arm from each subunit wraps around the dinucleotide-binding domain of an adjacent subunit, covering the adenine ring of NADP.Conclusions In GFOR, the NADP is found associated with a classical dinucleotide-binding domain in a conventional fashion. The NADP is effectively buried in the protein-subunit interior as a result of interactions with the N-terminal arm from an adjacent subunit in the tetramer, and with a short helix from the C-terminal domain of the protein. This accounts for NADP's inability to dissociate. The N-terminal arm may also contribute to stabilization of the tetramer. The enzyme has an unexpected structural similarity with the cytoplasmic enzyme glucose-6-phosphate dehydrogenase (G6PD). We hypothesize that both enzymes have diverged from a common ancestor. The mechanism of catalysis is still unclear, but we have identified a conserved structural motif (Glu–Lys–Pro) in the active site of GFOR and G6PD that may be important for catalysis

Crystal Structure of Spy0129, a Streptococcus pyogenes Class B Sortase Involved in Pilus Assembly

Sortase enzymes are cysteine transpeptidases that mediate the covalent attachment of substrate proteins to the cell walls of Gram-positive bacteria, and thereby play a crucial role in virulence, infection and colonisation by pathogens. Many cell-surface proteins are anchored by the housekeeping sortase SrtA but other more specialised sortases exist that attach sub-sets of proteins or function in pilus assembly. The sortase Spy0129, or SrtC1, from the M1 SF370 strain of Streptococcus pyogenes is responsible for generating the covalent linkages between the pilin subunits in the pili of this organism. The crystal structure of Spy0129 has been determined at 2.3 Å resolution (R = 20.4%, Rfree  = 26.0%). The structure shows that Spy0129 is a class B sortase, in contrast to other characterised pilin polymerases, which belong to class C. Spy0129 lacks a flap believed to function in substrate recognition in class C enzymes and instead has an elaborated β6/β7 loop. The two independent Spy0129 molecules in the crystal show differences in the positions and orientations of the catalytic Cys and His residues, Cys221 and His126, correlated with movements of the β7/β8 and β4/β5 loops that respectively follow these residues. Bound zinc ions stabilise these alternative conformations in the crystal. This conformational variability is likely to be important for function although there is no evidence that zinc is involved in vivo

Love Among the Roses

It was on one summer\u27s eveningin the merry month of JuneI beheld a damsel sitting \u27Mid flower\u27s sweet perfumeShe had a novel readingjust as I was passing byAnd as she turned another pageI saw the brightest eye A bewitching smile was on her faceAs charming as the posies I felt the smart of Cupid\u27s dart\u27Twas love among the roses. CHORUSNow I hate to tell but then I must,Within her heart I place my trustShe was sitting in the garden WHere the little butterlfy reposesAnd how we met,I\u27ll ne\u27er forgwet,\u27Twas Love among the Roses. Now I passed her house next eveningThe clock had just struck eightAnd I saw my future happinessShe was standing by the garden gateShe smile as I approached herAnd I begged her to excuse May I view those pretty flowers She murmured if you chooseI spoke about the violetsThen finally made proposesThro\u27 the garden we walked of happiness talked\u27Twas love among the roses. I confess I love Matilda,Matilda, that\u27s her name,And there is a charm about her Which I never can explain She dresses up to fashion To her style there is no endAnd of course she must look dashingFor she wears a Grecian Bend But she\u27s left her home and where she\u27s goneMost everyone supposes For as dear as life is my little wife\u27Twas love among the roses

Structures of Mycobacterium tuberculosis folylpolyglutamate synthase complexed with ADP and AMPPCP

Crystal structures of M. tuberculosis folylpolyglutamate synthetase complexed with two nucleotides have been determined at 2.0 and 2.3 Å resolution, revealing an active-site loop movement and associated changes that influence substrate binding

Noninvasive vagus nerve stimulation alters neural response and physiological autonomic tone to noxious thermal challenge.

The mechanisms by which noninvasive vagal nerve stimulation (nVNS) affect central and peripheral neural circuits that subserve pain and autonomic physiology are not clear, and thus remain an area of intense investigation. Effects of nVNS vs sham stimulation on subject responses to five noxious thermal stimuli (applied to left lower extremity), were measured in 30 healthy subjects (n = 15 sham and n = 15 nVNS), with fMRI and physiological galvanic skin response (GSR). With repeated noxious thermal stimuli a group × time analysis showed a significantly (p < .001) decreased response with nVNS in bilateral primary and secondary somatosensory cortices (SI and SII), left dorsoposterior insular cortex, bilateral paracentral lobule, bilateral medial dorsal thalamus, right anterior cingulate cortex, and right orbitofrontal cortex. A group × time × GSR analysis showed a significantly decreased response in the nVNS group (p < .0005) bilaterally in SI, lower and mid medullary brainstem, and inferior occipital cortex. Finally, nVNS treatment showed decreased activity in pronociceptive brainstem nuclei (e.g. the reticular nucleus and rostral ventromedial medulla) and key autonomic integration nuclei (e.g. the rostroventrolateral medulla, nucleus ambiguous, and dorsal motor nucleus of the vagus nerve). In aggregate, noninvasive vagal nerve stimulation reduced the physiological response to noxious thermal stimuli and impacted neural circuits important for pain processing and autonomic output

Mercury Orbiter: Report of the Science Working Team

The results are presented of the Mercury Orbiter Science Working Team which held three workshops in 1988 to 1989 under the auspices of the Space Physics and Planetary Exploration Divisions of NASA Headquarters. Spacecraft engineering and mission design studies at the Jet Propulsion Lab were conducted in parallel with this effort and are detailed elsewhere. The findings of the engineering study, summarized herein, indicate that spin stabilized spacecraft carrying comprehensive particles and fields experiments and key planetology instruments in high elliptical orbits can survive and function in Mercury orbit without costly sun shields and active cooling systems