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An asymmetric SMC–kleisin bridge in prokaryotic condensin
Bü,rmann, Frank,Shin, Ho-Chul,Basquin, Jé,rô,me,Soh, Young-Min,Gimé,nez-Oya, Victor,Kim, Yeon-Gil,Oh, Byung-Ha,Gruber, Stephan Nature Publishing Group, a division of Macmillan P 2013 Nature structural & molecular biology Vol.20 No.3
Eukaryotic structural maintenance of chromosomes (SMC)–kleisin complexes form large, ring-shaped assemblies that promote accurate chromosome segregation. Their asymmetric structural core comprises SMC heterodimers that associate with both ends of a kleisin subunit. However, prokaryotic condensin Smc–ScpAB is composed of symmetric Smc homodimers associated with the kleisin ScpA in a postulated symmetrical manner. Here, we demonstrate that Smc molecules have two distinct binding sites for ScpA. The N terminus of ScpA binds the Smc coiled coil, whereas the C terminus binds the Smc ATPase domain. We show that in Bacillus subtilis cells, an Smc dimer is bridged by a single ScpAB to generate asymmetric tripartite rings analogous to eukaryotic SMC complexes. We define a molecular mechanism that ensures asymmetric assembly, and we conclude that the basic architecture of SMC–kleisin rings evolved before the emergence of eukaryotes.
Molecular Basis for SMC Rod Formation and Its Dissolution upon DNA Binding
Soh, Young-Min,Bü,rmann, Frank,Shin, Ho-Chul,Oda, Takashi,Jin, Kyeong ,Sik,Toseland, Christopher ,P.,Kim, Cheolhee,Lee, Hansol,Kim, Soo ,Jin,Kong, Min-Seok,Durand-Diebold, Marie-Laure Cell Press 2015 Molecular cell Vol.57 No.2
<▼1><P><B>Summary</B></P><P>SMC condensin complexes are central modulators of chromosome superstructure in all branches of life. Their SMC subunits form a long intramolecular coiled coil, which connects a constitutive “hinge” dimerization domain with an ATP-regulated “head” dimerization module. Here, we address the structural arrangement of the long coiled coils in SMC complexes. We unequivocally show that prokaryotic Smc-ScpAB, eukaryotic condensin, and possibly also cohesin form rod-like structures, with their coiled coils being closely juxtaposed and accurately anchored to the hinge. Upon ATP-induced binding of DNA to the hinge, however, Smc switches to a more open configuration. Our data suggest that a long-distance structural transition is transmitted from the Smc head domains to regulate Smc-ScpAB’s association with DNA. These findings uncover a conserved architectural theme in SMC complexes, provide a mechanistic basis for Smc’s dynamic engagement with chromosomes, and offer a molecular explanation for defects in Cornelia de Lange syndrome.</P></▼1><▼2><P><B>Highlights</B></P><P>•<P>Prokaryotic Smc-ScpAB complexes form rod-like structures</P>•<P>Binding of ATP and DNA induces a rod-to-ring transition in prokaryotic condensin</P>•<P>The condensin hinge is rigidly anchored to its coiled coil</P>•<P>The rod-like conformation is a conserved feature of SMC protein dimers</P></P></▼2><▼3><P>Soh et al. show that the rod-like conformation is a conserved architectural scheme of SMC complexes. Upon ATP-induced binding to DNA, the juxtaposed coiled coils of prokaryotic Smc-ScpAB adopt an open conformation to expose a DNA binding site at the inner surface of the hinge domain.</P></▼3>
Varea, Olga,Martin-de-Saavedra, Maria Dolores,Kopeikina, Katherine J.,Schü,rmann, Britta,Fleming, Hunter J.,Fawcett-Patel, Jessica M.,Bach, Anthony,Jang, Seil,Peles, Elior,Kim, Eunjoon,Penzes, P National Academy of Sciences 2015 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.112 No.19
<P><B>Significance</B></P><P>In this paper, we characterize, for the first time to our knowledge, synaptic phenotypes in contactin associated protein-like 2 (<I>Cntnap2</I>) knockout neurons and reveal a novel role for CNTNAP2 in the correct trafficking of AMPA-type glutamate receptors. In addition, we report that cellular phenotypes emerge late in postnatal development, suggesting a mechanism for the apparent late emergence of some <I>CNTNAP2</I>-associated disorders. Taken together, our findings may provide insight into the mechanism underlying pathogenesis of <I>CNTNAP2</I>-associated neuropsychiatric disorders.</P><P>Central glutamatergic synapses and the molecular pathways that control them are emerging as common substrates in the pathogenesis of mental disorders. Genetic variation in the contactin associated protein-like 2 (<I>CNTNAP2</I>) gene, including copy number variations, exon deletions, truncations, single nucleotide variants, and polymorphisms have been associated with intellectual disability, epilepsy, schizophrenia, language disorders, and autism. CNTNAP2, encoded by <I>Cntnap2</I>, is required for dendritic spine development and its absence causes disease-related phenotypes in mice. However, the mechanisms whereby CNTNAP2 regulates glutamatergic synapses are not known, and cellular phenotypes have not been investigated in <I>Cntnap2</I> knockout neurons. Here we show that CNTNAP2 is present in dendritic spines, as well as axons and soma. Structured illumination superresolution microscopy reveals closer proximity to excitatory, rather than inhibitory synaptic markers. CNTNAP2 does not promote the formation of synapses and cultured neurons from <I>Cntnap2</I> knockout mice do not show early defects in axon and dendrite outgrowth, suggesting that CNTNAP2 is not required at this stage. However, mature neurons from knockout mice show reduced spine density and levels of GluA1 subunits of AMPA receptors in spines. Unexpectedly, knockout neurons show large cytoplasmic aggregates of GluA1. Here we characterize, for the first time to our knowledge, synaptic phenotypes in <I>Cntnap2</I> knockout neurons and reveal a novel role for CNTNAP2 in GluA1 trafficking. Taken together, our findings provide insight into the biological roles of CNTNAP2 and into the pathogenesis of <I>CNTNAP2</I>-associated neuropsychiatric disorders.</P>
Khachatryan, V.,Sirunyan, A. M.,Tumasyan, A.,Adam, W.,Bergauer, T.,Dragicevic, M.,Erö,, J.,Friedl, M.,Frü,hwirth, R.,Ghete, V. M.,Hartl, C.,Hö,rmann, N.,Hrubec, J.,Jeitler, M.,Kiesenhofer, Springer Berlin Heidelberg 2015 European Physical Journal C Vol.75 No.7
<P>Stringent limits are set on the long-lived lepton-like sector of the phenomenological minimal supersymmetric standard model (pMSSM) and the anomaly-mediated supersymmetry breaking (AMSB) model. The limits are derived from the results presented in a recent search for long-lived charged particles in proton–proton collisions, based on data collected by the CMS detector at a centre-of-mass energy of 8 TeV at the Large Hadron Collider. In the pMSSM parameter sub-space considered, 95.9 % of the points predicting charginos with a lifetime of at least 10 ns are excluded. These constraints on the pMSSM are the first obtained at the LHC. Charginos with a lifetime greater than 100 ns and masses up to about 800 GeV in the AMSB model are also excluded. The method described can also be used to set constraints on other models.</P>
Khachatryan, V.,Sirunyan, A. M.,Tumasyan, A.,Adam, W.,Bergauer, T.,Dragicevic, M.,Erö,, J.,Friedl, M.,Frü,hwirth, R.,Ghete, V. M.,Hartl, C.,Hö,rmann, N.,Hrubec, J.,Jeitler, M.,Kiesenhofer, Springer Berlin Heidelberg 2015 European Physical Journal C Vol.75 No.7
<P>This paper presents distributions of topological observables in inclusive three- and four-jet events produced in pp collisions at a centre-of-mass energy of 7[FORMULA OMISSION] with a data sample collected by the CMS experiment corresponding to a luminosity of 5.1[FORMULA OMISSION]. The distributions are corrected for detector effects, and compared with several event generators based on two- and multi-parton matrix elements at leading order. Among the considered calculations, <SMALL>MADGRAPH</SMALL> interfaced with <SMALL>PYTHIA6</SMALL> displays the overall best agreement with data.</P>
Probing color coherence effects in pp collisions at [FORMULA OMISSION]
Chatrchyan, S.,Khachatryan, V.,Sirunyan, A. M.,Tumasyan, A.,Adam, W.,Bergauer, T.,Dragicevic, M.,Erö,, J.,Fabjan, C.,Friedl, M.,Frü,hwirth, R.,Ghete, V. M.,Hö,rmann, N.,Hrubec, J.,Jeitler, Springer Berlin Heidelberg 2014 European Physical Journal C Vol.74 No.6
<P>A study of color coherence effects in pp collisions at a center-of-mass energy of 7[FORMULA OMISSION] is presented. The data used in the analysis were collected in 2010 with the CMS detector at the LHC and correspond to an integrated luminosity of 36 pb[FORMULA OMISSION]. Events are selected that contain at least three jets and where the two jets with the largest transverse momentum exhibit a back-to-back topology. The measured angular correlation between the second- and third-leading jet is shown to be sensitive to color coherence effects, and is compared to the predictions of Monte Carlo models with various implementations of color coherence. None of the models describe the data satisfactorily.</P>
Khachatryan, V.,Sirunyan, A. M.,Tumasyan, A.,Adam, W.,Bergauer, T.,Dragicevic, M.,Erö,, J.,Friedl, M.,Frü,hwirth, R.,Ghete, V. M.,Hartl, C.,Hö,rmann, N.,Hrubec, J.,Jeitler, M.,Kiesenhofer, Institute of Physics Pub 2015 The journal of high energy physics Vol.2015 No.5
<P>Searches for supersymmetry (SUSY) are performed using a sample of hadronic events produced in 8 TeV pp collisions at the CERN LHC. The searches are based on the M-T2 variable, which is a measure of the transverse momentum imbalance in an event. The data were collected with the CMS detector and correspond to an integrated luminosity of 19.5 fb(-1). Two related searches are performed. The first is an inclusive search based on signal regions defined by the value of the M-T2 variable, the hadronic energy in the event, the jet multiplicity, and the number of jets identified as originating from bottom quarks. The second is a search for a mass peak corresponding to a Higgs boson decaying to a bottom quark-antiquark pair, where the Higgs boson is produced as a decay product of a SUSY particle. For both searches, the principal backgrounds are evaluated with data control samples. No significant excess over the expected number of background events is observed, and exclusion limits on various SUSY models are derived.</P>
Khachatryan, V.,Sirunyan, A. M.,Tumasyan, A.,Adam, W.,Bergauer, T.,Dragicevic, M.,Erö,, J.,Friedl, M.,Frü,hwirth, R.,Ghete, V. M.,Hartl, C.,Hö,rmann, N.,Hrubec, J.,Jeitler, M.,Kiesenhofer, Springer Berlin Heidelberg 2015 European Physical Journal C Vol.75 No.5
<P>Properties of the Higgs boson with mass near 125[FORMULA OMISSION] are measured in proton-proton collisions with the CMS experiment at the LHC. Comprehensive sets of production and decay measurements are combined. The decay channels include [FORMULA OMISSION], [FORMULA OMISSION], [FORMULA OMISSION], [FORMULA OMISSION], [FORMULA OMISSION], and [FORMULA OMISSION] pairs. The data samples were collected in 2011 and 2012 and correspond to integrated luminosities of up to 5.1[FORMULA OMISSION] at 7[FORMULA OMISSION] and up to 19.7[FORMULA OMISSION] at 8[FORMULA OMISSION]. From the high-resolution [FORMULA OMISSION] and [FORMULA OMISSION] channels, the mass of the Higgs boson is determined to be [FORMULA OMISSION]. For this mass value, the event yields obtained in the different analyses tagging specific decay channels and production mechanisms are consistent with those expected for the standard model Higgs boson. The combined best-fit signal relative to the standard model expectation is [FORMULA OMISSION] at the measured mass. The couplings of the Higgs boson are probed for deviations in magnitude from the standard model predictions in multiple ways, including searches for invisible and undetected decays. No significant deviations are found.</P>
Khachatryan, V.,Sirunyan, A. M.,Tumasyan, A.,Adam, W.,Bergauer, T.,Dragicevic, M.,Erö,, J.,Fabjan, C.,Friedl, M.,Frü,hwirth, R.,Ghete, V. M.,Hartl, C.,Hö,rmann, N.,Hrubec, J.,Jeitler, M.,K Springer Berlin Heidelberg 2015 European Physical Journal C Vol.75 No.5
<P>This paper presents a measurement of the inclusive 3-jet production differential cross section at a proton–proton centre-of-mass energy of 7 TeV using data corresponding to an integrated luminosity of 5[FORMULA OMISSION]collected with the CMS detector. The analysis is based on the three jets with the highest transverse momenta. The cross section is measured as a function of the invariant mass of the three jets in a range of 445–3270 GeV and in two bins of the maximum rapidity of the jets up to a value of 2. A comparison between the measurement and the prediction from perturbative QCD at next-to-leading order is performed. Within uncertainties, data and theory are in agreement. The sensitivity of the observable to the strong coupling constant [FORMULA OMISSION] is studied. A fit to all data points with 3-jet masses larger than 664 GeV gives a value of the strong coupling constant of [FORMULA OMISSION].</P>
Search for microscopic black holes in pp collisions at $ \sqrt{s}=8 $ TeV
Chatrchyan, S.,Khachatryan, V.,Sirunyan, A. M.,Tumasyan, A.,Adam, W.,Bergauer, T.,Dragicevic, M.,Erö,, J.,Fabjan, C.,Friedl, M.,Frü,hwirth, R.,Ghete, V. M.,Hö,rmann, N.,Hrubec, J.,Jeitler, Springer-Verlag 2013 Journal of high energy physics Vol.2013 No.7