Crystal Structure of the p53 Core Domain Bound to a Full Consensus Site as a Self-Assembled Tetramer

SummaryRecent studies suggest that p53 binds predominantly to consensus sites composed of two decameric half-sites with zero spacing in vivo. Here we report the crystal structure of the p53 core domain bound to a full consensus site as a tetramer at 2.13Å resolution. Comparison with previously reported structures of p53 dimer:DNA complexes and a chemically trapped p53 tetramer:DNA complex reveals that DNA binding by the p53 core domain is a cooperative self-assembling process accompanied by structural changes of the p53 dimer and DNA. Each p53 monomer interacts with its two neighboring subunits through two different protein-protein interfaces. The DNA is largely B-form and shows no discernible bend, but the central base-pairs between the two half-sites display a significant slide. The extensive protein-protein and protein-DNA interactions explain the high cooperativity and kinetic stability of p53 binding to contiguous decameric sites and the conservation of such binding-site configuration in vivo

Abundance gradients in the galactic disk

The relationship between abundances and orbital parameters for 235 F- and G-type intermediate- and low- mass stars in the Galaxy is analyzed. We found that there are abundance gradients in the thin disk in both radial and vertical directions (-0.116 dex/kpc and -0.309 dex/kpc respectively). The gradients appear to be flatter as the Galaxy evolves. No gradient is found in the thick disk based on 18 thick disk stars. These results indicate that the ELS model is mainly suitable for the evolution of the thin disk, while the SZ model is more suitable for the evolution of the thick disk. Additionally, these results indicate that in-fall and out-flow processes play important roles in the chemical evolution of the Galaxy.Comment: 10 pages, 2 figures. Published in Science in China (Series G) vol 46(1), 200

Coupling of Cell Surface Biotinylation and SILAC-Based Quantitative Proteomics Identified Myoferlin as a Potential Therapeutic Target for Nasopharyngeal Carcinoma Metastasis

Distant metastasis is a major cause of treatment failure in nasopharyngeal carcinoma (NPC) patients. Cell surface proteins represent attractive targets for cancer diagnosis or therapy. However, the cell surface proteins associated with NPC metastasis are poorly understood. To identify potential therapeutic targets for NPC metastasis, we isolated cell surface proteins from two isogenic NPC cell lines, 6-10B (low metastatic) and 5-8F (highly metastatic), through cell surface biotinylation. Stable isotope labeling by amino acids in cell culture (SILAC) based proteomics was applied to comprehensively characterize the cell surface proteins related with the metastatic phenotype. We identified 294 differentially expressed cell surface proteins, including the most upregulated protein myoferlin (MYOF), two receptor tyrosine kinases(RTKs) epidermal growth factor receptor (EGFR) and ephrin type-A receptor 2 (EPHA2) and several integrin family molecules. These differentially expressed proteins are enriched in multiple biological pathways such as the FAK-PI3K-mTOR pathway, focal adhesions, and integrin-mediated cell adhesion. The knockdown of MYOF effectively suppresses the proliferation, migration and invasion of NPC cells. Immunohistochemistry analysis also showed that MYOF is associated with NPC metastasis. We experimentally confirmed, for the first time, that MYOF can interact with EGFR and EPHA2. Moreover, MYOF knockdown could influence not only EGFR activity and its downstream epithelial–mesenchymal transition (EMT), but also EPHA2 ligand-independent activity. These findings suggest that MYOF might be an attractive potential therapeutic target that has double effects of simultaneously influencing EGFR and EPHA2 signaling pathway. In conclusion, this is the first study to profile the cell surface proteins associated with NPC metastasis and provide valuable resource for future researches

Chiral topological metals with multiple types of quasiparticle fermions and large spin Hall effect in the SrGePt family materials

We present a prediction of chiral topological metals with several classes of unconventional quasiparticle fermions in a family of SrGePt-type materials in terms of first-principles calculations. In these materials, fourfold spin-3/2 Rarita-Schwinger-Weyl (RSW) fermion, sixfold excitation, and Weyl fermions coexist around the Fermi level as spin-orbit coupling is considered, and the Chern number for the first two kinds of fermions is the maximal value four. We found that large Fermi arcs from spin-3/2 RSW fermion emerge on the (010)-surface, spanning the whole surface Brillouin zone. Moreover, there exist Fermi arcs originating from Weyl points, which further overlap with trivial bulk bands. In addition, we revealed that the large spin Hall conductivity can be obtained, which attributed to the remarkable spin Berry curvature around the degenerate nodes and band-splitting induced by spin-orbit coupling. Our findings indicate that the SrGePt family of compounds provide an excellent platform for studying on topological electronic states and the intrinsic spin Hall effect.Comment: 10 pages and 7 figures in the main tex