Modular detergents tailor the purification and structural analysis of membrane proteins including G-protein coupled receptors

Detergents enable the purification of membrane proteins and are indispensable reagents instructural biology. Even though a large variety of detergents have been developed in the lastcentury, the challenge remains to identify guidelines that allowfine-tuning of detergents forindividual applications in membrane protein research. Addressing this challenge, here weintroduce the family of oligoglycerol detergents (OGDs). Native mass spectrometry (MS)reveals that the modular OGD architecture offers the ability to control protein purificationand to preserve interactions with native membrane lipids during purification. In addition to abroad range of bacterial membrane proteins, OGDs also enable the purification and analysisof a functional G-protein coupled receptor (GPCR). Moreover, given the modular design ofthese detergents, we anticipatefine-tuning of their properties for specific applications instructural biology. Seen from a broader perspective, this represents a significant advance forthe investigation of membrane proteins and their interactions with lipids

Switchable synchronisation of pirouetting motions in a redox-active [3]rotaxane

In this study, the crown/ammonium [3]rotaxane R2 is reported which allows a switchable synchronisation of wheel pirouetting motions. The rotaxane is composed of a dumbbell-shaped axle molecule with two mechanically interlocked macrocycles which are decorated with a redox-active tetrathiafulvalene (TTF) unit. Electrochemical, spectroscopic, and electron paramagnetic resonance experiments reveal that rotaxane R2 can be reversibly switched between four stable oxidation states (R2, R2˙+, R22(˙+), and R24+). The oxidations enable non-covalent, cofacial interactions between the TTF units in each state—including a stabilised mixed-valence (TTF2)˙+ and a radical-cation (TTF˙+)2 dimer interaction—which dictate a syn (R2, R2˙+, and R22(˙+)) or anti (R24+) ground state co-conformation of the wheels in the rotaxane. Furthermore, the strength of these wheel–wheel interactions varies with the oxidation state, and thus electrochemical switching allows a controllable synchronisation of the wheels’ pirouetting motions. DFT calculations explore the potential energy surface of the counter-rotation of the two interacting wheels in all oxidation states. The controlled coupling of pirouetting motions in rotaxanes can lead to novel molecular gearing systems which transmit rotational motion by switchable non-covalent interactions

Modular detergents tailor the purification and structural analysis of membrane proteins including G-protein coupled receptors

Detergents enable the purification of membrane proteins and are indispensable reagents in structural biology. Even though a large variety of detergents have been developed in the last century, the challenge remains to identify guidelines that allow fine-tuning of detergents for individual applications in membrane protein research. Addressing this challenge, here we introduce the family of oligoglycerol detergents (OGDs). Native mass spectrometry (MS) reveals that the modular OGD architecture offers the ability to control protein purification and to preserve interactions with native membrane lipids during purification. In addition to a broad range of bacterial membrane proteins, OGDs also enable the purification and analysis of a functional G-protein coupled receptor (GPCR). Moreover, given the modular design of these detergents, we anticipate fine-tuning of their properties for specific applications in structural biology. Seen from a broader perspective, this represents a significant advance for the investigation of membrane proteins and their interactions with lipids

Study of the Stabilization to the Nanometer Level of Mechanical Vibrations of the CLIC Main Beam

Original publication available at http://www.jacow.org/International audienceTo reach the design luminosity of CLIC, the movements of the quadrupoles should be limited to the nanometre level in order to limit the beam size and emittance growth. Below 1 Hz, the movements of the main beam quadrupoles will be corrected by a beambased feedback. But above 1 Hz, the quadrupoles should be mechanically stabilized. A collaboration effort is ongoing between several institutes to study the feasibility of the "nanostabilization" of the CLIC quadrupoles. The study described in this paper covers the characterization of independent measuring techniques including optical methods to detect nanometre sized displacements and analyze the vibrations. Actuators and feedback algorithms for sub-nanometre movements of magnets with a mass of more than 400 kg are being developed and tested. Input is given to the design of the quadrupole magnets, the supports and alignment system in order to limit the amplification of the vibration sources at resonant frequencies. A full scale mock-up integrating all these features is presently under design. Finally, a series of experiments in accelerator environments should demonstrate the feasibility of the nanometre stabilization

Superconducting Magnets for a Final Focus Upgrade of ATF2

Original publication available at http://www.jacow.org/International audienceThe Accelerator Test Facility 2 (ATF2) at KEK is a scaled version of the final focus (FF) design proposed for a future linear collider (LC). A primary ATF2 goal is to experimentally verify the FF technology needed to obtain very small, stable beam spots at an LC interaction point [1]. Initially the ATF2 FF is made using conventional (warm) quadrupole and sextupole magnets. We intend to upgrade the ATF2 FF by replacing conventional magnets with new superconducting ones that use the same technology proposed for the International Linear Collider (ILC) baseline FF magnets [2]. With this upgrade we can investigate smaller interaction point beta-functions and study superconducting magnet vibration stability in an accelerator environment. Our ATF2 magnet cryostat design incorporates features to facilitate monitoring of the cold mass movement via interferometric techniques. The status and future plans for the ATF2 superconducting magnet upgrade are reported here

Improved Measurement of the Positive Muon Anomalous Magnetic Moment

A new measurement of the positive muon's anomalous magnetic moment has been made at the Brookhaven Alternating Gradient Synchrotron using the direct injection of polarized muons into the superferric storage ring. The angular frequency difference omega_{a} between the angular spin precession frequency omega_{s} and the angular orbital frequency omega_{c} is measured as well as the free proton NMR frequency omega_{p}. These determine R = omega_{a} / omega_{p} = 3.707~201(19) times 10^{-3}. With mu_{mu} / mu_{p} = 3.183~345~39(10) this gives a_{mu^+} = 11~659~191(59) times 10^{-10} (pm 5 ppm), in good agreement with the previous CERN and BNL measurements for mu^+ and mu^-, and with the standard model prediction.Comment: 4 pages, 4 figures. accepted for publication in Phys. Rev. D62 Rapid Communication

Search for Lorentz and CPT Violation Effects in Muon Spin Precession

The spin precession frequency of muons stored in the $(g-2)$ storage ring has been analyzed for evidence of Lorentz and CPT violation. Two Lorentz and CPT violation signatures were searched for: a nonzero $\Delta\omega_{a}$ (=$\omega_{a}^{\mu^{+}}-\omega_{a}^{\mu^{-}}$); and a sidereal variation of $\omega_{a}^{\mu^{\pm}}$. No significant effect is found, and the following limits on the standard-model extension parameters are obtained: $b_{Z} =-(1.0 \pm 1.1)\times 10^{-23}$ GeV; $(m_{\mu}d_{Z0}+H_{XY}) = (1.8 \pm 6.0 \times 10^{-23})$ GeV; and the 95% confidence level limits $\check{b}_{\perp}^{\mu^{+}}< 1.4 \times 10^{-24}$ GeV and $\check{b}_{\perp}^{\mu^{-}} < 2.6 \times 10^{-24}$ GeV.Comment: 5 pages, 3 figures, submitted to Physical Review Letters, Modified to answer the referees suggestion

An Improved Limit on the Muon Electric Dipole Moment

Three independent searches for an electric dipole moment (EDM) of the positive and negative muons have been performed, using spin precession data from the muon g-2 storage ring at Brookhaven National Laboratory. Details on the experimental apparatus and the three analyses are presented. Since the individual results on the positive and negative muon, as well as the combined result, d=-0.1(0.9)E-19 e-cm, are all consistent with zero, we set a new muon EDM limit, |d| < 1.9E-19 e-cm (95% C.L.). This represents a factor of 5 improvement over the previous best limit on the muon EDM.Comment: 19 pages, 15 figures, 7 table

Search for Lorentz and CPT Violation Effects in Muon Spin Precession

The spin precession frequency of muons stored in the $(g-2)$ storage ring has been analyzed for evidence of Lorentz and CPT violation. Two Lorentz and CPT violation signatures were searched for: a nonzero $\Delta\omega_{a}$ (=$\omega_{a}^{\mu^{+}}-\omega_{a}^{\mu^{-}}$); and a sidereal variation of $\omega_{a}^{\mu^{\pm}}$. No significant effect is found, and the following limits on the standard-model extension parameters are obtained: $b_{Z} =-(1.0 \pm 1.1)\times 10^{-23}$ GeV; $(m_{\mu}d_{Z0}+H_{XY}) = (1.8 \pm 6.0 \times 10^{-23})$ GeV; and the 95% confidence level limits $\check{b}_{\perp}^{\mu^{+}}< 1.4 \times 10^{-24}$ GeV and $\check{b}_{\perp}^{\mu^{-}} < 2.6 \times 10^{-24}$ GeV.Comment: 5 pages, 3 figures, submitted to Physical Review Letters, Modified to answer the referees suggestion