Phosphorylated and Unphosphorylated Serine 13 of CDC37 Stabilize Distinct Interactions between Its Client and HSP90 Binding Domains

Folding and maturation of most protein kinases require chaperone assistance. In higher eukaryotes, CDC37 is the predominant cochaperone that facilitates the transfer of kinase clients to HSP90. Kinase recognition is thought to occur through the N-terminal domain, which has, thus far, eluded structure determination. Client processing also requires the phosphorylation of the N-terminal tail at Ser13 by protein kinase CK2 (casein kinase 2). How phosphorylation alters the molecular properties of CDC37 is not understood. We show that the phosphorylation at Ser13 induces a large shift toward a more compact structure, based on ANS fluorescence, while modestly increasing secondary structure. Moreover, this transition requires interactions of the N-terminal domain and the remainder of CDC37. The stabilizing property of the phosphorylation event can be recreated in trans by a (phospho-Ser13) peptide derived from the N-terminal tail. However, the phosphorylation-induced transition is not dependent on the transferred phosphate group but rather the loss of serine-like properties at position 13. The complete absence of the N-terminal tail results in reduced secondary structure and unresponsiveness to subsequent addition of peptides. The N-terminal tail may therefore serve as an intramolecular chaperone that ensures that CDC37 assumes one of two readily interconvertible states in a manner that impacts the interaction of the client binding N-domain and the MC-domains, involved in dimerization and HSP90 binding

Sterically Controlled Functionalization of Carbon Surfaces with −C₆H₄CH₂X (X = OSO₂Me or N₃) Groups for Surface Attachment of Redox-Active Molecules

Glassy carbon electrodes were modified by electrochemical reduction of a diazonium molecule (^<i>i</i>Pr₃SiOCH₂­C₆H₄N₂⁺BF₄^–) featuring a triisopropylsilyl-protected benzylic hydroxyl group. This electrochemical process introduced a monolayer of ^<i>i</i>Pr₃Si­OCH₂C₆H₄– groups onto the surface of the electrode. The bulky −Si^<i>i</i>Pr₃ protecting group not only prevents the uncontrolled growth of structurally ill-defined and electronically blocking polyphenylene multilayers, but also separates the phenyl groups in the monolayer. Thus, the void spaces between these aryl units should allow a better accommodation of sizable molecules. Removal of the −Si^<i>i</i>Pr₃ protecting groups by ^<i>n</i>Bu₄NF exposed the reactive benzylic hydroxyl functionalities that can undergo further transformations to anchor functional molecules. As an example, redox-active ferrocene molecules were grafted onto the modified electrode via a sequence of mesylation, azidation, and copper-catalyzed [3 + 2] cycloaddition reactions. The presence of ferrocenyl groups on the surface was confirmed by X-ray photoelectron spectroscopic and electrochemical studies. The resulting ferrocene-modified glassy carbon electrode exhibits cyclic voltammograms typical of surface-bound redox active species and remarkable electrochemical stability in an acidic aqueous environment

Self-Assembly of Semiconductor Nanoparticles/Reduced Graphene Oxide (RGO) Composite Aerogels for Enhanced Photocatalytic Performance and Facile Recycling in Aqueous Photocatalysis

A BiOBr/reduced graphene oxide (RGO) composite aerogel with BiOBr nanoplates grown on an interconnected three-dimensional RGO-based porous network was prepared by one-pot hydrothermal method using l-lysine as a reducing agent and the cross-linker. Its enhanced adsorption toward pollutants owing to its large Brunauer–Emmett–Teller specific surface area and spongy nature, improved light absorption due to its extremely lightweight nature and the RGO promoting photogenerated charge separation contributed to the BiOBr/RGO aerogel’s enhanced activity for photocatalytic degradation in an aqueous system. The BiOBr/RGO aerogel also showed high stability and can be easily separated from the reaction systems for recycling. The facile one-pot method has been proved to be generic in the formations of different semiconductor embedded RGO aerogels like BiOX/RGO (X = Cl and I), CdS/RGO and Fe₂O₃/RGO aerogels, which combine the advantages of enhanced photocatalytic activity with facile recycling for applications in aqueous photocatalytic reaction systems

Ubiquitin ligases of the rat pineal gland whose expression is increased by dbcAMP^* or NE <i>in vitro</i>.

<p>Ubiquitin ligases of the rat pineal gland whose expression is increased by dbcAMP^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172441#t004fn001" target="_blank">*</a>} or NE <i>in vitro</i>.</p

A model of SIK1 function in the pineal gland.

<p>SIK1 –salt-inducible kinase 1; E1 –ubiquitin activating enzyme; E2 –ubiquitin conjugase; E3 –ubiquitin ligase; U—ubiquitin; PKA–protein kinase A; P–phosphate; DUB–deubiquitinase; UDB–ubiquitin binding domain; UBA–ubiquitin associated domain.</p

Ubiquitin Ligases of the rat pineal gland whose expression is increased at least 2-fold at night in the Hartley dataset.

<p>Ubiquitin Ligases of the rat pineal gland whose expression is increased at least 2-fold at night in the Hartley dataset.</p

B-adrenergic innervation and ubiquitin proteasome system regulation of AANAT and melatonin concentrations in the pineal gland.

<p>R—regulatory component of PKA; C—catalytic subunits of PKA; β - Beta adrenergic receptor; Ac—Adenyl cyclase; Gs—G stimulatory protein that activates adenyl cyclase; Praja2 –ubiquitin ligase coded for by <i>PJA2</i> gene; UCHL1—Ubiquitin C-terminal hydroxylase, a deubiquitinase enzyme; CREB—cyclic AMP response element binding protein; AANAT—aralkylamine N-acetyltransferase; U—ubiquitin; P–phosphate; 14-3-3ζ –a protein kinase inhibitor protein coded for by the <i>YWHAZ</i> gene</p

Ubiquitin ligases of the rat pineal gland whose expression is decreased at least 2-fold at night in the Hartley dataset.

<p>Ubiquitin ligases of the rat pineal gland whose expression is decreased at least 2-fold at night in the Hartley dataset.</p

Patch and ubiquitin proteasome system regulation of Dio2 in the pineal gland.

<p>SHH—Sonic Hedgehog Homolog protein; PTCH—patched homolog protein, a receptor for SHH; SMO—smoothened protein, a receptor that interacts with the PTCH receptor; GLI—glioma-associated oncogene protein, a transcription factor; WSB1 –WD repeat and SOCS box-containing protein, a ubiquitin ligase; DIO2 –type two deiodinase; USP33—ubiquitin specific peptidase 33, a deubiquitinase.</p

3D mapping of residual stresses in growing grains of partially recrystallized Gum Metal

The crystallographic orientations and residual stresses within recrystallizing grains in partially recrystallized β titanium—Gum Metal—were examined non-destructively in 3D using synchrotron Differential Aperture X-ray Microscopy. Contrary to common assumptions, significant local stresses and stress variations are observed within the recrystallizing grains. The results reveal that the development of these local residual stresses depends on the plastic deformation mode and material’s elastic constants, rather than grain properties such as size and orientation, or even the material’s yield stress. This work provides insights valuable for the design of advanced materials with heterogeneous microstructures.</p