Direct binding to sterols accelerates endoplasmic reticulum-associated degradation of HMG CoA reductase.

The maintenance of cholesterol homeostasis is crucial for normal function at both the cellular and organismal levels. Two integral membrane proteins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and Scap, are key targets of a complex feedback regulatory system that operates to ensure cholesterol homeostasis. HMGCR catalyzes the rate-limiting step in the transformation of the 2-carbon precursor acetate to 27-carbon cholesterol.

Regulated degradation of HMG CoA reductase requires conformational changes in sterol-sensing domain.

3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is the rate-limiting enzyme in cholesterol synthesis and target of cholesterol-lowering statin drugs. Accumulation of sterols in endoplasmic reticulum (ER) membranes accelerates degradation of HMGCR, slowing the synthesis of cholesterol. Degradation of HMGCR is inhibited by its binding to UBIAD1 (UbiA prenyltransferase domain-containing protein-1).

Thermodynamic Surface Analyses to Inform Biofilm Resistance.

Biofilms are the habitat of 95% of bacteria successfully protecting bacteria from many antibiotics. However, inhibiting biofilm formation is difficult in that it is a complex system involving the physical and chemical interaction of both substrate and bacteria. Focusing on the substrate surface and potential interactions with bacteria, we examined both physical and chemical properties of substrates coated with a series of phenyl acrylate monomer derivatives.

Endosomal sorting of Notch receptors through COMMD9-dependent pathways modulates Notch signaling.

Notch family members are transmembrane receptors that mediate essential developmental programs. Upon ligand binding, a proteolytic event releases the intracellular domain of Notch, which translocates to the nucleus to regulate gene transcription. In addition, Notch trafficking across the endolysosomal system is critical in its regulation.

Lipid-regulated degradation of HMG-CoA reductase and Insig-1 through distinct mechanisms in insect cells.

In mammalian cells, levels of the integral membrane proteins 3-hydroxy-3-methylglutaryl-CoA reductase and Insig-1 are controlled by lipid-regulated endoplasmic reticulum-associated degradation (ERAD). The ERAD of reductase slows a rate-limiting step in cholesterol synthesis and results from sterol-induced binding of its membrane domain to Insig-1 and the highly related Insig-2 protein. Insig binding bridges reductase to ubiquitin ligases that facilitate its ubiquitination, thereby marking the protein for cytosolic dislocation and proteasomal degradation.

The Surface of Nanoparticle Silicon as Studied by Solid-State NMR.

The surface structure and adjacent interior of commercially available silicon nanopowder (-Si) was studied using multinuclear, solid-state NMR spectroscopy. The results are consistent with an overall picture in which the bulk of the -Si consists of highly ordered ("crystalline") silicon atoms, each bound tetrahedrally to four other silicon atoms. From a combination of ¹H, Si and ²H magic-angle-spinning (MAS) NMR results and quantum mechanical Si chemical shift calculations, silicon atoms on the of "as-received" -Si were found to exist in a variety of chemical structures, with apparent populations in the order (a) (-O-)₃-H > (b) (-O-)₃OH > (c) (HO-)()(-O) ≈ (d) (-O-)₂(H)OH > (e) (-O-)₂(-OH)₂ > (f) (-O-)₄, where stands for a surface silicon atom and represents another silicon atom that is attached to by either a - bond or a -O- linkage.

Saving transverse magnetization.

A magnetization storage sequence, ALT-1 (alternating longitudinal and transverse components), is reported. The ALT-1 sequence is a hybrid of two types of storage sequences, the Carr-Purcell type and store-and-restore sequences. During incremental storage periods within the ALT-1 sequence, essentially half of the initially transverse magnetization is stored along the z-axis and the other half is prolonged by an echo-generating pulse.