Delineation of a unique protein-protein interaction site on the surface of the estrogen receptor

Recent studies have identified a series of estrogen receptor (ER)interacting peptides that recognize sites that are distinct from the classic coregulator recruitment (AF2) region. Here, we report the structural and functional characterization of an ER alpha-specific peptide that binds to the liganded receptor in an AF2-independent manner. The 2-angstrom crystal structure of the ER/peptide complex reveals a binding site that is centered on a shallow depression on the beta-hairpin face of the ligand-binding domain. The peptide binds in an unusual extended conformation and makes multiple contacts with the ligand-binding domain. The location and architecture of the binding site provides an insight into the peptide's ER subtype specificity and ligand interaction preferences. In vivo, an engineered coactivator containing the peptide motif is able to strongly enhance the transcriptional activity of liganded ER alpha, particularly in the presence of 4-hydroxytamoxifen. Furthermore, disruption of this binding surface alters ER's response to the coregulator TIF2. Together, these results indicate that this previously unknown interaction site represents a bona fide control surface involved in regulating receptor activity

Evidence for Factorization in Three-body B --> D(*) K- K0 Decays

Motivated by recent experimental results, we use a factorization approach to study the three-body B --> D(*) K- K0 decay modes. Two mechanisms are proposed for kaon pair production: current-produced (from vacuum) and transition (from B meson). The Bbar0 --> D(*)+ K- K0 decay is governed solely by the current-produced mechanism. As the kaon pair can be produced only by the vector current, the matrix element can be extracted from e+ e- --> K Kbar processes via isospin relations. The decay rates obtained this way are in good agreement with experiment. Both current-produced and transition processes contribute to B- --> D(*)0 K- K0 decays. By using QCD counting rules and the measured B- --> D(*)0 K- K0 decay rates, the measured decay spectra can be understood.Comment: 17 pages, 6 figure

Vir-Mir db: prediction of viral microRNA candidate hairpins

MicroRNAs have been found in various organisms and play essential roles in gene expression regulation of many critical cellular processes. Large-scale computational prediction of miRNAs has been conducted for many organisms using known genomic sequences; however, there has been no such effort for the thousands of known viral genomes. Some viruses utilize existing host cellular pathways for their own benefit. Furthermore, viruses are capable of encoding miRNAs and using them to repress host genes. Thus, identifying potential miRNAs in all viral genomes would be valuable to virologists who study virus–host interactions. Based on our previously reported hairpin secondary structure and feature selection filters, we have examined the 2266 available viral genome sequences for putative miRNA hairpins and identified 33 691 hairpin candidates in 1491 genomes. Evaluation of the system performance indicated that our discovery pipeline exhibited 84.4% sensitivity. We established an interface for users to query the predicted viral miRNA hairpins based on taxonomic classification, and a host target gene prediction service based on the RNAhybrid program and the 3′-UTR gene sequences of human, mouse, rat, zebrafish, rice and Arabidopsis. The viral miRNA prediction database (Vir-Mir) can be accessed via http://alk.ibms.sinica.edu.tw

Wafer-Bonded Internal Back-Surface Reflectors for Enhanced TPV Performance

This paper discusses recent efforts to realize GaInAsSb/GaSb TPV cells with an internal back-surface reflector (BSR). The cells are fabricated by wafer bonding the GaInAsSb/GaSb device layers to GaAs substrates with a dielectric/Au reflector, and subsequently removing the GaSb substrate. The internal BSR enhances optical absorption within the device while the dielectric layer provides electrical isolation. This approach is compatible with monolithic integration of series-connected TPV cells and can mitigate the requirements of filters used for front-surface spectral control

GaInAsSb/A1GaAsSb/Sb Thermophotovoltaic Devices With an Internal Back-Surface Reflector Formed by Wafer Bonding

A novel implementation for GAInAsSb/AlGaAsSb/GaSb TPV cells with an internal back-surface reflector (BSR) formed by wafer bonding to GaAs is demonstrated. The SiO{sub x}/Ti/Au internal BSR enhances optical absorption within the device, while the dielectric layer provides electrical isolation. This configuration has the potential to improve TPV device performance; is compatible with monolithic series-interconnection of TPV cells for building voltage; and can mitigate the requirements of filters used for front-surface spectral control. At a short-circuit density of 0.4 A/cm{sup 2}, the open-circuit voltage of a single TPV cell is 0.2 V, compared to 0.37 and 1.8 V for 2- and 10-junction series-interconnected TPV cells, respectively

Human ADA3 regulates RARα transcriptional activity through direct contact between LxxLL motifs and the receptor coactivator pocket

The alternation/deficiency in activation-3 (ADA3) is an essential component of the human p300/CBP-associated factor (PCAF) and yeast Spt-Ada-Gcn5-acetyltransferase (SAGA) histone acetyltransferase complexes. These complexes facilitate transactivation of target genes by association with transcription factors and modification of local chromatin structure. It is known that the yeast ADA3 is required for nuclear receptor (NR)-mediated transactivation in yeast cells; however, the role of mammalian ADA3 in NR signaling remains elusive. In this study, we have investigated how the human (h) ADA3 regulates retinoic acid receptor (RAR) α-mediated transactivation. We show that hADA3 interacts directly with RARα in a hormone-dependent manner and this interaction contributes to RARα transactivation. Intriguingly, this interaction involves classical LxxLL motifs in hADA3, as demonstrated by both ‘loss’ and ‘gain’ of function mutations, as well as a functional coactivator pocket of the receptor. Additionally, we show that hADA3 associates with RARα target gene promoter in a hormone-dependent manner and ADA3 knockdown impairs RARβ2 expression. Furthermore, a structural model was established to illustrate an interaction network within the ADA3/RARα complex. These results suggest that hADA3 is a bona fide transcriptional coactivator for RARα, acting through a conserved mechanism involving direct contacts between NR boxes and the receptor’s co-activator pocket

Wafer Bonding and Epitaxial Transfer of GaSb-based Epitaxy to GaAs for Monolithic Interconnection of Thermophotovoltaic Devices

GaInAsSb/AlGaAsSb/InAsSb/GaSb epitaxial layers were bonded to semi-insulating GaAs handle wafers with SiO{sub x}/Ti/Au as the adhesion layer for monolithic interconnection of thermophotovoltaic (TPV) devices. Epitaxial transfer was completed by removal of the GaSb substrate, GaSb buffer, and InAsSb etch-stop layer by selective chemical etching. The SiO{sub x}/TiAu provides not only electrical isolation, but also high reflectivity and is used as an internal back-surface reflector. Characterization of wafer-bonded epitaxy by high-resolution x-ray diffraction and time-decay photoluminescence indicates minimal residual stress and enhancement in optical quality. 0.54-eV GaInAsSb cells were fabricated and monolithically interconnected in series. A 10-junction device exhibited linear voltage building with an open-circuit voltage of 1.8 V