The crystal structure of a nucleic acid triplex reveals helix, designated P-form, that differs from previously reported structures. consists one polypurine DNA strand complexed to polypyrimidine hairpin peptide (PNA) and was successfully designed promote Watson-Crick Hoogsteen base pairing. P-form helix is underwound, with tilt similar B-form DNA. bases are displaced the axis even more than in A-form Hydrogen bonds between backbone PNA explain observation sequences form highly stable 2:1...

Significance Cystic fibrosis (CF) is caused by mutations in the cystic transmembrane conductance regulator ( CFTR ) gene, which codes for a chloride/bicarbonate channel whose absence leads to dehydration and acidification of CF airways. A contributing factor lung disease dysregulation epithelial Na + (ENaC), exacerbates mucus dehydration. Here, we show that ENaC hyperactivity airways direct consequence acidic airway surface liquid (ASL) ASL hydration restored raising pH. Additionally, short...

Clostridium perfringens enterotoxin is a common cause of food-borne and antibiotic-associated diarrhea. The toxin's receptors on intestinal epithelial cells include claudin-3 -4, members large family tight junction proteins. Toxin-induced cytolytic pore formation requires residues in the NH(2)-terminal half, whereas near COOH terminus are required for binding to claudins. claudin-binding COOH-terminal domain not toxic currently under investigation as potential drug absorption enhancer....

Members of the CsrA family prokaryotic mRNA-binding proteins alter translation and/or stability transcripts needed for numerous global physiological processes. The previously described member in Pseudomonas aeruginosa (RsmA) plays a central role determining infection modality by reciprocally regulating processes associated with acute (type III secretion and motility) chronic VI biofilm formation) infection. Here we describe second, structurally distinct RsmA homolog P. (RsmF) that has an...

Several regulators of G protein signaling (RGS) proteins contain a gamma-subunit-like (GGL) domain, which, as we have shown, binds to Gbeta5 subunits. Here, extend our original findings by describing another GGL-domain-containing RGS, human RGS6. When RGS6 is coexpressed with different Gbeta subunits, only and interact. The expression mRNA for in tissues overlaps. Predictions alpha-helical coiled-coil character within GGL domains, coupled measurements binding domain mutants, support the...

CIB1 (CIB) is an EF-hand-containing protein that binds multiple effector proteins, including the platelet alphaIIbbeta3 integrin and several serine/threonine kinases potentially modulates their function. The crystal structure for Ca(2+)-bound has been determined at 2.0 A resolution reveals a compact alpha-helical containing four EF-hands, last two of which bind calcium ions in standard fashion seen many other EF-hand proteins. shares high structural similarity with calcineurin B neuronal...

Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), a C-type lectin expressed on the plasma membrane by human immature dendritic cells, is receptor for numerous viruses including Ebola, SARS and dengue. A controversial question has been whether DC-SIGN functions as complete both binding internalization of dengue virus (DENV) or it solely cell surface attachment factor, requiring either hand-off to another co-receptor internalization. To examine this...

We study the problem of describing local components Néron–Tate height functions on abelian varieties over characteristic <inline-formula content-type="math/mathml"> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="0"> <mml:semantics> <mml:mn>0</mml:mn> <mml:annotation encoding="application/x-tex">0</mml:annotation> </mml:semantics> </mml:math> </inline-formula> fields as spaces torsors under various realisations alttext="2"> <mml:mn>2</mml:mn>...

Multidrug-resistant Staphylococcus aureus infections pose a significant threat to human health. Antibiotic resistance is most commonly propagated by conjugative plasmids like pLW1043, the first vancomycin-resistant S. vector identified in humans. We present molecular basis for transmission nicking enzyme (NES), which essential transfer. NES initiates and terminates transfer of that variously confer range drugs, including vancomycin, gentamicin, mupirocin. The N-terminal relaxase–DNA complex...

The enzyme dehaloperoxidase (DHP) from the terebellid polychaete Amphitrite ornata is a heme protein which has globin fold but can function as both hemoglobin and peroxidase. As peroxidase, DHP capable of converting 2,4,6-trihalophenols to corresponding 2,6-dihaloquinones in presence hydrogen peroxide. hemoglobin, cycles between oxy deoxy states it reversibly binds oxygen for storage. Here, reported that distal histidine, His55, exhibits conformational flexibility form consequently observed...

We report two crystal structures, each at a resolution of 2.8 Å, recombinant human fibrinogen fragment D (rfD) in the absence and presence peptide ligands. The bound ligands, Gly-Pro-Arg-Pro-amide Gly-His-Arg-Pro-amide, mimic interactions thrombin exposed polymerization sites, "A" "B", respectively. This is first to describe structure both structures reveal that nearly identical plasma protein but with minor changes, like addition proximal fucose carbohydrate linked residue βGln364, slightly...

Most mammalian cell types depend on multiple Src family kinases (SFKs) to regulate diverse signaling pathways. Strict control of SFK activity is essential for normal cellular function, and loss kinase regulation contributes several forms cancer other diseases. Previous x-ray crystal structures the SFKs c-Src Hck revealed that intramolecular association their homology (SH) 3 domains SH2 linker regions has a key role in down-regulation activity. However, amino acid sequence represents...

Detailed structural comparisons of sperm-specific glyceraldehyde 3-phosphate dehydrogenase, spermatogenic (GAPDHS) and the somatic dehydrogenase (GAPDH) isozyme should facilitate identification selective GAPDHS inhibitors for contraceptive development. This study identified a small-molecule inhibitor with micromolar potency >10-fold selectivity that exerts expected inhibitory effects on sperm glycolysis motility. Glycolytic ATP production is required motility male fertility in many mammalian...

Abstract The chief barrier to studies of how genetic coding emerged is the lack experimental models for ancestral aminoacyl-tRNA synthetases (AARS). We hypothesized that conserved core catalytic sites could represent such ancestors. That hypothesis enabled engineering functional “urzymes” from TrpRS, LeuRS, and HisRS. describe here a fourth urzyme, GlyCA, detected in an open reading frame genomic record arctic fox, Vulpes lagopus . GlyCA homologous bacterial heterotetrameric Class II...

Abstract The hypothesis that conserved core catalytic sites could represent ancestral aminoacyl-tRNA synthetases (AARS) drove the design of functional TrpRS, LeuRS, and HisRS ‘urzymes’. We describe here new urzymes detected in genomic record arctic fox, Vulpes lagopus. They are homologous to α-subunit bacterial heterotetrameric Class II glycyl-tRNA synthetase (GlyRS-B) enzymes. AlphaFold2 predicted N-terminal 81 amino acids would adopt a 3D structure nearly identical our designed urzyme...

G protein-coupled receptors mediate cellular responses to a wide variety of stimuli, including taste, light, and neurotransmitters. In the yeast Saccharomyces cerevisiae, activation pheromone pathway triggers events leading mating. The view had long been held that protein-mediated signal occurs principally at plasma membrane. Recently, it has shown protein alpha subunit Gpa1 can promote signaling endosomes requires two components sole phosphatidylinositol-3-kinase in yeast, Vps15 Vps34....

Chloroplast mRNAs in Euglena gracilis fall into two classes. One class has a Shine-Dalgarno sequence 5' to the AUG start codon while other group of does not have any conserved elements near codon. The chloroplast mRNA encoding atpH gene been selected as an example message which (GGAGUU) located initiation region. Mutations result 2-5-fold reductions efficiency complex formation depending on precise mutation. Secondary structure mapping region suggests that number conformations are present...