Paul Scherrer Institute

About: Paul Scherrer Institute is a facility organization based out in Villigen, Switzerland. It is known for research contribution in the topics: Neutron & Large Hadron Collider. The organization has 9248 authors who have published 23984 publications receiving 890129 citations. The organization is also known as: PSI.

The structural basis of agonist-induced activation in constitutively active rhodopsin

Abstract: Structural studies of active states of the visual pigment rhodopsin, a G protein-coupled receptor, have previously been limited to apoprotein or opsin forms that do not contain the agonist all-trans-retinal. Two groups now report structures that reveal more details of the transformations involved in rhodopsin activation. Choe et al. solve the X-ray crystal structure of the metarhodopsin II intermediate of the photoreceptor rhodopsin, and Standfuss et al. determine the structure of a constitutively active mutant of rhodopsin bound to a peptide derived from the C-terminus of the G protein transducin. This study solves the X-ray crystal structure of a constitutively active mutant of rhodopsin, a G-protein-coupled receptor, bound to a peptide derived from the C-terminus of the G protein transducin. Comparison of this structure with the structure of ground-state rhodopsin suggests how translocation of the retinal β-ionone ring leads to a rotational tilt of transmembrane helix 6, the critical conformational change that occurs upon activation. G-protein-coupled receptors (GPCRs) comprise the largest family of membrane proteins in the human genome and mediate cellular responses to an extensive array of hormones, neurotransmitters and sensory stimuli. Although some crystal structures have been determined for GPCRs, most are for modified forms, showing little basal activity, and are bound to inverse agonists or antagonists. Consequently, these structures correspond to receptors in their inactive states. The visual pigment rhodopsin is the only GPCR for which structures exist that are thought to be in the active state1,2. However, these structures are for the apoprotein, or opsin, form that does not contain the agonist all-trans retinal. Here we present a crystal structure at a resolution of 3 A for the constitutively active rhodopsin mutant Glu 113 Gln3,4,5 in complex with a peptide derived from the carboxy terminus of the α-subunit of the G protein transducin. The protein is in an active conformation that retains retinal in the binding pocket after photoactivation. Comparison with the structure of ground-state rhodopsin6 suggests how translocation of the retinal β-ionone ring leads to a rotation of transmembrane helix 6, which is the critical conformational change on activation7. A key feature of this conformational change is a reorganization of water-mediated hydrogen-bond networks between the retinal-binding pocket and three of the most conserved GPCR sequence motifs. We thus show how an agonist ligand can activate its GPCR.

Heterogeneous photochemistry in the atmosphere.

Abstract: Atmospheric aerosols can be categorized into primary particles, which are directly emitted by their sources, and secondary particles, generated in the atmosphere from gaseous inorganic and organic precursors. For example, atmospheric oxidation of sulfur containing compounds leads to sulfuric acid and its salts, which represent a major secondary inorganic component of atmospheric aerosols. Likewise, oxidation of nitrogen oxides leads to nitric acid or its salts, which are also abundant in aerosols. The ocean surface, which covers three-quarters of the planet, offers a remarkably dynamic and chemically complex surface for interfacial reactions in the marine boundary layer. The porous nature of permanent or perennial snowpacks adds a tremendous amount of surface area, with which the atmosphere interacts. In short, solar radiation can provide the energy to initiate reactions while atmospherically available surfaces or condensed phases may act to reduce the required energy for a given photochemical pathway, for instance, by allowing a longer wavelength for reaction of species associated with a surface or bulk phase environment.

The PILATUS 1M detector.

Abstract: The PILATUS 1M detector is a hybrid pixel array detector with over one million pixels that operate in single photon counting mode. The detector, designed for macromolecular crystallography, is the largest pixel array detector currently in use at a synchrotron. It is a modular system consisting of 18 multichip modules covering an area of 21 cm × 24 cm. The design of the components as well as the manufacturing of the detector including the bump-bonding was performed at the Paul Scherrer Institute (PSI). The use of a single photon counting detector for protein crystallography requires detailed studies of the charge collection properties of the silicon sensor. The 18 modules are read out in parallel, leading to a full frame readout-time of 6.7 ms. This allows crystallographic data to be acquired in fine-φ-slicing mode with continuous rotation of the sample. The detector was tested in several experiments at the protein crystallography beamline X06SA at the Swiss Light Source at PSI. Data were collected both in conventional oscillation mode using the shutter, as well as in a fine-φ-slicing mode. After applying all the necessary corrections to data from a thaumatin crystal, the processing of the conventional data led to satisfactory merging R-factors of the order of 8.5%. This allows, for the first time, determination of a refined electron density map of a macromolecular biological crystal using a silicon pixel detector.

Transverse-Momentum and Pseudorapidity Distributions of Charged Hadrons in pp Collisions at root s=7 TeV

Abstract: Charged-hadron transverse-momentum and pseudorapidity distributions in proton-proton collisions at root s = 7 TeV are measured with the inner tracking system of the CMS detector at the LHC. The charged-hadron yield is obtained by counting the number of reconstructed hits, hit pairs, and fully reconstructed charged-particle tracks. The combination of the three methods gives a charged-particle multiplicity per unit of pseudorapidity dN(ch)/d eta vertical bar(vertical bar eta vertical bar<0.5) = 5.78 +/- 0.01(stat) +/- 0.23(stat) for non-single-diffractive events, higher than predicted by commonly used models. The relative increase in charged-particle multiplicity from root s = 0.9 to 7 TeV is [66.1 +/- 1.0(stat) +/- 4.2(syst)]%. The mean transverse momentum is measured to be 0.545 +/- 0.005(stat) +/- 0.015(syst) GeV/c. The results are compared with similar measurements at lower energies.

SASfit: a tool for small-angle scattering data analysis using a library of analytical expressions

Abstract: SASfit is one of the mature programs for small-angle scattering data analysis and has been available for many years. This article describes the basic data processing and analysis workflow along with recent developments in the SASfit program package (version 0.94.6). They include (i) advanced algorithms for reduction of oversampled data sets, (ii) improved confidence assessment in the optimized model parameters and (iii) a flexible plug-in system for custom user-provided models. A scattering function of a mass fractal model of branched polymers in solution is provided as an example for implementing a plug-in. The new SASfit release is available for major platforms such as Windows, Linux and MacOS. To facilitate usage, it includes comprehensive indexed documentation as well as a web-based wiki for peer collaboration and online videos demonstrating basic usage. The use of SASfit is illustrated by interpretation of the small-angle X-ray scattering curves of monomodal gold nanoparticles (NIST reference material 8011) and bimodal silica nanoparticles (EU reference material ERM-FD-102).