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Abstract: We present the crystal structure of an immunoglobulin light-chain-like domain, CTLA-4, as a strand-swapped dimer displaying cis–trans proline isomerisation and native-like hydrogen bonding. We also show that CTLA-4 can form amyloid-like fibres and amorphous deposits explainable by the same strand swapping. Our results suggest a molecular basis for the pathological aggregation of immunoglobulin domains and why amyloid-like fibres are more often composed of homologous rather than heterologous subunits.
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Jun 2010
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Abstract: NGFI-B is a ligand-independent orphan nuclear receptor of the NR4A subfamily that displays important functional differences with its homolog Nurr1. In particular, the NGFI-B ligand-binding domain (LBD) exhibits only modest activity in cell lines in which the Nurr1 LBD strongly activates transcription. To gain insight into the structural basis for the distinct activation potentials, we determined the crystal structure of the NGFI-B LBD at 2.4-Å resolution. Superimposition with the Nurr1 LBD revealed a significant shift of the position of helix 12, potentially caused by conservative amino acids exchanges in helix 3 or helix 12. Replacement of the helix 11–12 region of Nurr1 with that of NGFI-B dramatically reduces the transcriptional activity of the Nurr1 LBD. Similarly, mutation of Met414 in helix 3 to leucine or of Leu591 in helix 12 to isoleucine (the corresponding residues found in NGFI-B) significantly affects Nurr1 transactivation. In comparison, swapping the helix 11–12 region of Nurr1 into NGFI-B results in a modest increase of activity. These observations reveal a high sensitivity of LBD activity to changes that influence helix 12 positioning. Furthermore, mutation of hydrophobic surface residues in the helix 11–12 region (outside the canonical co-activator surface constituted by helices 3, 4, and 12) severely affects Nurr1 transactivation. Together, our data suggest that a novel co-regulator surface that includes helix 11 and a specifically positioned helix 12 determine the cell type-dependent activities of the NGFI-B and the Nurr1 LBD.
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Feb 2005
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Abstract: Recent, primarily structural observations indicate that related viruses, harboring no sequence similarity, infect hosts of different domains of life. One such clade of viruses, defined by common capsid architecture and coat protein fold, is the so-called PRD1-adenovirus lineage. Here we report the structure of the marine lipid-containing bacteriophage PM2 determined by crystallographic analyses of the entire similar to 45 MDa virion and of the outer coat proteins P1 and P2, revealing PM2 to be a primeval member of the PRD1-adenovirus lineage with an icosahedral, shell and canonical double beta barrel major coat protein. The view of the lipid bilayer, richly decorated with membrane proteins, constitutes a rare visualization of an in vivo membrane. The viral membrane proteins P3 and P6 are organized into a lattice, suggesting a possible assembly pathway to produce the mature virus.
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Jan 2008
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Abstract: The ordering of block copolymers in thin films is reviewed, starting from the fundamental principles and extending to recent promising developments as templates for nanolithography which may find important applications in the semiconductor industry. Ordering in supported thin films of symmetric and asymmetric AB diblock and ABA triblock copolymers is discussed, along with that of more complex materials such as ABC triblocks and liquid crystalline block copolymers. Techniques to prepare thin films, and to characterise ordering within them, are summarized. Several methods to align block copolymer nanostructures, important in several applications are outlined. A number of potential applications in nanolithography, production of porous materials, templating, and patterning of organic and inorganic materials are then presented. The influence of crystallization on the morphology of a block copolymer film is briefly discussed, as are structures in grafted block copolymer films.
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Nov 2009
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Abstract: The polydentate ligand 2,4,6-tris(dipyridin-2-ylamino)-1,3,5-triazine (dpyatriz) in combination with the Cu(ClO4)2/CuX2 salt mixtures (X? = Cl?, Br?, or N3?) leads to the formation of molecular coordination aggregates with formulas [Cu3Cl3(dpyatriz)2](ClO4)3 (2), [Cu3Br3(dpyatriz)2](ClO4)3 (3), and [Cu4(N3)4(dpyatriz)2(DMF)4(ClO4)2](ClO4)2 (4). These complexes consist of two dpyatriz ligands bridged via coordination to CuII and disposed either face-to-face in an eclipsed manner (2 and 3) or parallel and mutually shifted in one direction. The copper ions complete their coordination positions with Cl? (2), Br? (3), or N3?, ClO4?, and N,N-dimethylformamide (DMF) (4) ligands. All complexes crystallize together with noncoordinate ClO4? groups that display anion···? interactions with the triazine rings. These interactions have been studied by means of high level ab initio calculations and the MIPp partition scheme. These calculations have proven the ClO4?···[C3N3] interactions to be favorable and have revealed a synergistic effect from the combined occurrence of ??? stacking of triazine rings and the interaction of these moieties with perchlorate ions, as observed in the experimental systems.
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May 2008
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Oriano
Francescangeli
,
Vesna
Stanic
,
Sofia
Torgova
,
Alfredo
Strigazzi
,
Nicola
Scaramuzza
,
Claudio
Ferrero
,
Igor
Dolbnya
,
Thomas
Weiss
,
Roberto
Berardi
,
Luca
Muccioli
,
Silvia
Orlandi
,
Claudio
Zannoni
Abstract: The still undiscovered fluid ferroelectric nematic phase is expected to exhibit a much faster and easier response to an external electric field compared to conventional ferroelectric smectic liquid crystals; therefore, the discovery of such a phase could open new avenues in electro-optic device technology. Here, experimental evidence of a ferroelectric response to a switching electric field in a low molar mass nematic liquid crystal is reported and connected with field-induced biaxiality. The fluid is made of bent-core polar molecules and is nematic over a range of 120 °C. Combining repolarization current measurements, electro-optical characterizations, X-ray diffraction and computer simulations, ferroelectric switching is demonstrated and it is concluded that the response is due to field-induced reorganization of polar cybotactic groups within the nematic phase. This work represents significant progress toward the realization of ferroelectric fluids that can be aligned at command with a simple electric field.
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Aug 2009
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Abstract: We describe the synthesis, crystal structure and conducting properties of two new BEDT-TTF charge transfer salts of tris(oxalato)ferrate(III) containing slightly different numbers of water molecules, (BEDT-TTF)12[Fe(C2O4)3]2·xH2O [x = 15 (I) and 16 (II)]. I crystallizes in the monoclinic space groupC2/c, a = 36.017(10), b = 30.880(10), c = 36.183(15) Å, ? = 90, ? = 93.66(3), ? = 90°, V = 40161(23) Å3, T = 120(2) K, Z = 8, R1 = 0.0842 [F2 > 2?(F2)]; II crystallizes in the same space group, a = 17.9695(15), b = 15.4988(13), c = 36.115(3) Å, ? = 90, ? = 93.720(2), ? = 90°, V = 10037.1(14) Å3, T = 150(2) K, Z = 4, R1 = 0.0673 [F2 > 2?(F2)]. Electrical resistivity measurements show that I and II are semiconductors below 275 K.
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Oct 2007
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Feb 2009
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Diamond Proposal Number(s):
[442]
Abstract: Protein structure determination of soluble globular protein domains has developed into an efficient routine technology which can now be applied to generate and analyze structures of entire human protein families. In the kinase area, several kinase families still lack comprehensive structural analysis. Nevertheless, Structural Genomics (SG) efforts contributed more than 40 kinase catalytic domain structures during the past 4 years providing a rich resource of information for large scale comparisons of kinase active sites. Moreover, many of the released structures are inhibitor complexes that offer chemical starting points for development of selective and potent inhibitors. Here we discuss the currently available structural data and strategies that can be utilized for the development of highly selective inhibitors.
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Mar 2010
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Abstract: The phase diagram of a series of poly(1,2-octylene oxide)–poly(ethylene oxide) (POO–PEO) diblock copolymers is determined by small-angle X-ray scattering. The Flory–Huggins interaction parameter was measured by small-angle neutron scattering. The phase diagram is highly asymmetric due to large conformational asymmetry that results from the hexyl side chains in the POO block. Non-lamellar phases (hexagonal and gyroid) are observed near fPEO?=?0.5, and the lamellar phase is observed for fPEO???0.5.
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Nov 2009
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