NMR and mutational identification of the collagen-binding site of the chaperone Hsp47.

Heat shock protein 47 (Hsp47) acts as a client-specific chaperone for collagen and plays a vital role in collagen maturation and the consequent embryonic development. In addition, this protein can be a potential target for the treatment of fibrosis. Despite its physiological and pathological importance, little is currently known about the collagen-binding mode of Hsp47 from a structural aspect. Here, we describe an NMR study that was conducted to identify the collagen-binding site of Hsp47. We used chicken Hsp47, which has higher solubility than its human counterpart, and applied a selective (15)N-labeling method targeting its tryptophan and histidine residues. Spectral assignments were made based on site-directed mutagenesis of the individual residues. By inspecting the spectral changes that were observed upon interaction with a trimeric collagen peptide and the mutational data, we successfully mapped the collagen-binding site in the B/C β-barrel domain and a nearby loop in a 3D-homology model based upon a serpin fold. This conclusion was confirmed by mutational analysis. Our findings provide a molecular basis for the design of compounds that target the interaction between Hsp47 and procollagen as therapeutics for fibrotic diseases

Pressure-induced structural phase transition and new superconducting phase in UTe2

We report on the crystal structure and electronic properties of the heavy fermion superconductor UTe2 at high pressure up to 11 GPa, as investigated by X-ray diffraction and electrical resistivity experiments. The X-ray diffraction measurements under high pressure using a synchrotron light source reveal anisotropic linear compressibility of the unit cell up to 3.5 GPa, while a pressure-induced structural phase transition is observed above 3.5-4GPa at room temperature, where the body-centered orthorhombic crystal structure with the space group Immm changes into a body-centered tetragonal structure with the space group I4/mmm. The molar volume drops abruptly at the critical pressure, while the distance between the first-nearest neighbor of U atoms increases, implying a switch from the heavy electronic states to the weakly correlated electronic states. Surprisingly, a new superconducting phase at pressures higher than 7 GPa was detected at Tsc above 2K with a relatively low upper-critical field, Hc2(0). The resistivity above 3.5GPa, thus, in the high-pressure tetragonal phase, shows a large drop below 230 K, which may also be related to a considerable change from the heavy electronic states to the weakly correlated electronic states.Comment: 11 pages, 9 figure

First Observation of de Haas-van Alphen Effect and Fermi Surfaces in Unconventional Superconductor UTe2

We report the first observation of the de Haas-van Alphen (dHvA) effect in the novel spin-triplet superconductor UTe2 using high quality single crystals with the high residual resistivity ratio (RRR) over 200. The dHvA frequencies, named alpha and beta, are detected for the field directions between c and a-axes. The frequency of branch beta increases rapidly with the field angle tilted from c to a-axis, while branch alpha splits, owing to the maximal and minimal cross-sectional areas from the same Fermi surface. Both dHvA branches, alpha and beta reveal two kinds of cylindrical Fermi surfaces with a strong corrugation at least for branch alpha. The angular dependence of the dHvA frequencies is in very good agreement with that calculated by the generalized gradient approximation (GGA) method taking into account the on-site Coulomb repulsion of U = 2 eV, indicating the main Fermi surfaces are experimentally detected. The detected cyclotron effective masses are large in the range from 32 to 57 m0 . They are approximately 10-20 times lager than the corresponding band masses, consistent with the mass enhancement obtained from the Sommerfeld coefficient and the calculated density of states at the Fermi level. The local density approximation (LDA) calculations of ThTe2 assuming U4+ with the 5f^2 localized model are in less agreement with our experimental results, in spite of the prediction for two cylindrical Fermi surfaces, suggesting a mixed valence states of U4+ and U3+ in UTe2.Comment: 7 pages, 8 figures, submitted to J. Phys. Soc. Jp