Investigation of the thermodynamic drivers of the interaction between the high mobility group box domain of Sox2 and bacterial lipopolysaccharide.

Gastric cancer is associated with high mortality and is preceded by an infection with Helicobacter pylori (H. pylori). H.

Somatic loss of PIK3R1 may sensitize breast cancer to inhibitors of the MAPK pathway.

Purpose: The PI3K pathway, which includes the PI3K catalytic subunits p110α (PIK3CA) and the PI3K regulatory subunit p85α (PIK3R1), is the most frequently altered pathway in cancer. We encountered a breast cancer patient whose tumor contained a somatic alteration in PIK3R1. Some commercial sequencing platforms suggest that somatic mutations in PIK3R1 may sensitize cancers to drugs that inhibit the mammalian target of rapamycin (mTOR).

Mechanism of Mitochondrial Transcription Factor A Attenuation of CpG-Induced Antibody Production.

Mitochondrial transcription factor A (TFAM) had previously been shown to act as a damage associated molecular pattern with the ability to enhance CpG-A phosphorothioate oligodeoxynucleotide (ODN)-mediated stimulation of IFNα production from human plasmacytoid dendritic cells. Examination of the mechanism by which TFAM might influence CpG ODN mediated innate immune responses revealed that TFAM binds directly, tightly and selectively to the structurally related CpG-A, -B, and -C ODN. TFAM also modulated the ability of the CpG-B or -C to stimulate the production of antibodies from human B cells.

The sea urchin mitochondrial transcription factor A binds and bends DNA efficiently despite its unusually short C-terminal tail.

Mitochondrial transcription factor A (TFAM) is a key component for the protection and transcription of the mitochondrial genome. TFAM belongs to the high mobility group (HMG) box family of DNA binding proteins that are able to bind to and bend DNA. Human TFAM (huTFAM) contains two HMG box domains separated by a linker region, and a 26 amino acid C-terminal tail distal to the second HMG box.

Binding of the histone chaperone ASF1 to the CBP bromodomain promotes histone acetylation.

The multifunctional Creb-binding protein (CBP) protein plays a pivotal role in many critical cellular processes. Here we demonstrate that the bromodomain of CBP binds to histone H3 acetylated on lysine 56 (K56Ac) with higher affinity than to its other monoacetylated binding partners. We show that autoacetylation of CBP is critical for the bromodomain-H3 K56Ac interaction, and we propose that this interaction occurs via autoacetylation-induced conformation changes in CBP.

Reversed-phase ion-pair liquid chromatography method for purification of duplex DNA with single base pair resolution.

Obtaining quantities of highly pure duplex DNA is a bottleneck in the biophysical analysis of protein-DNA complexes. In traditional DNA purification methods, the individual cognate DNA strands are purified separately before annealing to form DNA duplexes. This approach works well for palindromic sequences, in which top and bottom strands are identical and duplex formation is typically complete.

The high mobility group box: the ultimate utility player of a cell.

High mobility group (HMG) box proteins are abundant and ubiquitous DNA binding proteins with a remarkable array of functions throughout the cell. The structure of the HMG box DNA binding domain and general mechanisms of DNA binding and bending have been known for more than a decade. However, new mechanisms that regulate HMG box protein intracellular translocation, and by which HMG box proteins recognize DNA with and without sequence specificity, have only recently been uncovered.

Transcriptional activation by mitochondrial transcription factor A involves preferential distortion of promoter DNA.

Mitochondrial transcription factor A (mtTFA/TFAM) is a nucleus-encoded, high-mobility-group-box (HMG-box) protein that regulates transcription of the mitochondrial genome by specifically recognizing light-strand and heavy-strand promoters (LSP, HSP1). TFAM also binds mitochondrial DNA in a non-sequence specific (NSS) fashion and facilitates its packaging into nucleoid structures. However, the requirement and contribution of DNA-bending for these two different binding modes has not been addressed in detail, which prompted this comparison of binding and bending properties of TFAM on promoter and non-promoter DNA.

Evidence for two distinct Mg2+ binding sites in G(s alpha) and G(i alpha1) proteins.

The function of guanine nucleotide binding (G) proteins is Mg(2+) dependent with guanine nucleotide exchange requiring higher metal ion concentration than guanosine 5'-triphosphate hydrolysis. It is unclear whether two Mg(2+) binding sites are present or if one Mg(2+) binding site exhibits different affinities for the inactive GDP-bound or the active GTP-bound conformations. We used furaptra, a Mg(2+)-specific fluorophore, to investigate Mg(2+) binding to alpha subunits in both conformations of the stimulatory (G(s alpha)) and inhibitory (G(i alpha1)) regulators of adenylyl cyclase.