Deciphering the folding kinetics of transmembrane helical proteins

Nearly a quarter of genomic sequences and almost half of all receptors that are likely to be targets for drug design are integral membrane proteins. Understanding the detailed mechanisms of the folding of membrane proteins is a largely unsolved, key problem in structural biology. Here, we introduce a general model and use computer simulations to study the equilibrium properties and the folding kinetics of a $C_{\alpha}$-based two helix bundle fragment (comprised of 66 amino-acids) of Bacteriorhodopsin. Various intermediates are identified and their free energy are calculated toghether with the free energy barrier between them. In 40% of folding trajectories, the folding rate is considerably increased by the presence of non-obligatory intermediates acting as traps. In all cases, a substantial portion of the helices is rapidly formed. This initial stage is followed by a long period of consolidation of the helices accompanied by their correct packing within the membrane. Our results provide the framework for understanding the variety of folding pathways of helical transmembrane proteins

Biogenesis of mitochondrial porin

We review here the present knowledge about the pathway of import and assembly of porin into mitochondria and compare it to those of other mitochondrial proteins. Porin, like all outer mitochondrial membrane proteins studied so far is made as a precursor without a cleavble lsquosignalrsquo sequence; thus targeting information must reside in the mature sequence. At least part of this information appears to be located at the amino-terminal end of the molecule. Transport into mitochondria can occur post-translationally. In a first step, the porin precursor is specifically recognized on the mitochondrial surface by a protease sensitive receptor. In a second step, porin precursor inserts partially into the outer membrane. This step is mediated by a component of the import machinery common to the import pathways of precursor proteins destined for other mitochondrial subcompartments. Finally, porin is assembled to produce the functional oligomeric form of an integral membrane protein wich is characterized by its extreme protease resistance

Identification of particles with Lorentz factor up to 10410^{4} with Transition Radiation Detectors based on micro-strip silicon detectors

This work is dedicated to the study of a technique for hadron identification in the TeV momentum range, based on the simultaneous measurement of the energies and of the emission angles of the Transition Radiation (TR) X-rays with respect to the radiating particles. A detector setup has been built and tested with particles in a wide range of Lorentz factors (from about $10^3$ to about $4 \times 10^4$ crossing different types of radiators. The measured double-differential (in energy and angle) spectra of the TR photons are in a reasonably good agreement with TR simulation predictions.Comment: 31 pages, 12 figures, paper published on Nuclear Instruments & Methods

Performance of 4096 pixel photon counting chip

A 4096 pixel Photon Counting Chip (PCC) has been developed and tested. It is aimed primarily at medical imaging although it can be used for other applications involving particle counting. The readout chip consists of a matrix of 64 x 64 identical square pixels, whose side measures 170 mm and is bump-bonded to a similar matrix of GaAs or Si pixel diodes covering a sensitive area of 1.18 cm . The electronics in each cell comprises a preamplifier, a discriminator with variable threshold and a 3-bit threshold tune as well as 15-bit counter. Each pixel can be individually addressed for electrical test or masked during acquisition. A shutter allows for switching between the counting and the readout modes and the use of a static logic in the counter enables long data taking periods. Electrical tests of the chip have shown a maximum counting rate of up to 2 MHz in each pixel. The minimum reachable threshold is 1400 e with a variation of 350 e rms that can be reduced to 80 e rms after tuning with the 3-bit adjustment. Electical noise at the input is 170 e rms. Several read-out chips have been bump-bonded to 200 mm thick GaAs detectors. Tests with g-rays and b sources have been carried out. A number of objects have been imaged and 260 mm thick aluminium foil which represents a contrast to the surrounding aire of only 1.9% has been correctly imaged

The nucleotide and partial amino acid sequences of rat fetuin

Fetuins are among the major plasma proteins, yet their biological role has remained elusive. Here we report the molecular cloning of rat fetuin and the sequence analysis of a full-length clone, RF619 of 1456 bp with an open reading frame of 1056 bp encoding 352 amino acid residues. The coding part of RF619 was identical with the cDNA sequence of the natural inhibitor of the insulin receptor tyrosine kinase from rat (pp63) except for four substitutions and a single base insertion causing divergence of the predicted protein sequences. Partial amino acid sequences of rat plasma fetuin were in agreement with the predictions based on the RF619 cDNA. Purified rat fetuin inhibited the insulin receptor tyrosine kinase in vitro. Therefore, we conclude that RF619 and pp63 cDNA encode the same protein, i.e. authentic rat fetuin which is a functional tyrosine kinase inhibitor

Measurements of the branching fractions of B+→ppK+ decays

The branching fractions of the decay B+ → pp̄K+ for different intermediate states are measured using data, corresponding to an integrated luminosity of 1.0 fb-1, collected by the LHCb experiment. The total branching fraction, its charmless component Mpp̄ < 2.85 GeV/c2 and the branching fractions via the resonant cc̄ states η c(1S) and ψ(2S) relative to the decay via a J/ψ intermediate state are [Equation not available: see fulltext.] Upper limits on the B + branching fractions into the η c(2S) meson and into the charmonium-like states X(3872) and X(3915) are also obtained

Search for the rare decays B0→J/ψγB^{0}\to J/\psi \gamma and Bs0→J/ψγB^{0}_{s} \to J/\psi \gamma

A search for the rare decay of a $B^{0}$ or $B^{0}_{s}$ meson into the final state $J/\psi\gamma$ is performed, using data collected by the LHCb experiment in $pp$ collisions at $\sqrt{s}=7$ and $8$ TeV, corresponding to an integrated luminosity of 3 fb$^{-1}$. The observed number of signal candidates is consistent with a background-only hypothesis. Branching fraction values larger than $1.7\times 10^{-6}$ for the $B^{0}\to J/\psi\gamma$ decay mode are excluded at 90% confidence level. For the $B^{0}_{s}\to J/\psi\gamma$ decay mode, branching fraction values larger than $7.4\times 10^{-6}$ are excluded at 90% confidence level, this is the first branching fraction limit for this decay.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-044.htm

A model-independent confirmation of the Z(4430)−Z(4430)^- state

The decay $B^0\to \psi(2S) K^+\pi^-$ is analyzed using $\rm 3~fb^{-1}$ of $pp$ collision data collected with the LHCb detector. A model-independent description of the $\psi(2S) \pi$ mass spectrum is obtained, using as input the $K\pi$ mass spectrum and angular distribution derived directly from data, without requiring a theoretical description of resonance shapes or their interference. The hypothesis that the $\psi(2S)\pi$ mass spectrum can be described in terms of $K\pi$ reflections alone is rejected with more than 8$\sigma$ significance. This provides confirmation, in a model-independent way, of the need for an additional resonant component in the mass region of the $Z(4430)^-$ exotic state.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-038.htm

Differential branching fraction and angular analysis of Λb0→Λμ+μ−\Lambda^{0}_{b} \rightarrow \Lambda \mu^+\mu^- decays

The differential branching fraction of the rare decay $\Lambda^{0}_{b} \rightarrow \Lambda \mu^+\mu^-$ is measured as a function of $q^{2}$, the square of the dimuon invariant mass. The analysis is performed using proton-proton collision data, corresponding to an integrated luminosity of 3.0 \mbox{ fb}^{-1}, collected by the LHCb experiment. Evidence of signal is observed in the $q^2$ region below the square of the $J/\psi$ mass. Integrating over 15 < q^{2} < 20 \mbox{ GeV}^2/c^4 the branching fraction is measured as d\mathcal{B}(\Lambda^{0}_{b} \rightarrow \Lambda \mu^+\mu^-)/dq^2 = (1.18 ^{+ 0.09} _{-0.08} \pm 0.03 \pm 0.27) \times 10^{-7} ( \mbox{GeV}^{2}/c^{4})^{-1}, where the uncertainties are statistical, systematic and due to the normalisation mode, $\Lambda^{0}_{b} \rightarrow J/\psi \Lambda$, respectively. In the $q^2$ intervals where the signal is observed, angular distributions are studied and the forward-backward asymmetries in the dimuon ($A^{l}_{\rm FB}$) and hadron ($A^{h}_{\rm FB}$) systems are measured for the first time. In the range 15 < q^2 < 20 \mbox{ GeV}^2/c^4 they are found to be A^{l}_{\rm FB} = -0.05 \pm 0.09 \mbox{ (stat)} \pm 0.03 \mbox{ (syst)} and A^{h}_{\rm FB} = -0.29 \pm 0.07 \mbox{ (stat)} \pm 0.03 \mbox{ (syst)}.Comment: 27 pages, 10 figures, Erratum adde

Evidence for the strangeness-changing weak decay Ξb−→Λb0π−\Xi_b^-\to\Lambda_b^0\pi^-

Using a $pp$ collision data sample corresponding to an integrated luminosity of 3.0~fb$^{-1}$, collected by the LHCb detector, we present the first search for the strangeness-changing weak decay $\Xi_b^-\to\Lambda_b^0\pi^-$. No $b$ hadron decay of this type has been seen before. A signal for this decay, corresponding to a significance of 3.2 standard deviations, is reported. The relative rate is measured to be ${{f_{\Xi_b^-}}\over{f_{\Lambda_b^0}}}{\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-) = (5.7\pm1.8^{+0.8}_{-0.9})\times10^{-4}$, where $f_{\Xi_b^-}$ and $f_{\Lambda_b^0}$ are the $b\to\Xi_b^-$ and $b\to\Lambda_b^0$ fragmentation fractions, and ${\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)$ is the branching fraction. Assuming $f_{\Xi_b^-}/f_{\Lambda_b^0}$ is bounded between 0.1 and 0.3, the branching fraction ${\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-)$ would lie in the range from $(0.57\pm0.21)\%$ to $(0.19\pm0.07)\%$.Comment: 7 pages, 2 figures, All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-047.htm