Search results for " Tertiary"
showing 10 items of 349 documents
A genetic variant of the atrial natriuretic peptide gene is associated with cardiometabolic protection in the general community
2011
Objectives We sought to define the cardiometabolic phenotype associated with rs5068, a genetic variant of the atrial natriuretic peptide (ANP) gene. Background The ANP and B-type natriuretic peptide play an important role in cardiorenal homeostasis but also exert metabolic actions. Methods We genotyped 1,608 randomly selected residents from Olmsted County, Minnesota. Subjects were well-characterized. Results Genotype frequencies were: AA 89.9%, AG 9.7%, and GG 0.4%; all subsequent analyses were AA versus AG+GG. The G allele was associated with increased plasma levels of N-terminal pro-atrial natriuretic peptide (p = 0.002), after adjustment for age and sex. The minor allele was also associa…
Endothelialization of chitosan porous conduits via immobilization of a recombinant fibronectin fragment (rhFNIII7–10)
2013
Abstract The present study aimed to develop a pre-endothelialized chitosan (CH) porous hollowed scaffold for application in spinal cord regenerative therapies. CH conduits with different degrees of acetylation (DA; 4% and 15%) were prepared, characterized (microstructure, porosity and water uptake) and functionalized with a recombinant fragment of human fibronectin (rhFNIII 7–10 ). Immobilized rhFNIII 7–10 was characterized in terms of amount ( 125 I-radiolabelling), exposure of cell-binding domains (immunofluorescence) and ability to mediate endothelial cell (EC) adhesion and cytoskeletal rearrangement. Functionalized conduits revealed a linear increase in immobilized rhFNIII 7–10 with rhF…
Ancient or recent? Insights into the temporal evolution of the Bruniaceae
2008
AbstractThe Bruniaceae are a South African plant family endemic to the Cape Floristic Region with one geographic outlier (Raspalia trigyna) in the Natal Province. Recent molecular phylogenetic analyses have cast new light upon inter- and intra-generic relationships within the family. The present work uses those data to gain insights into the temporal evolution of Bruniaceae by inferring a molecular clock. For calibration, the inferred age of Berzelia cordifolia (3–5My) was used, based on its distribution restricted to the geologically young limestone area around Bredasdorp. The results are consistent with the purported Cretaceous age of the family (‘palaeoendemics’), but also suggest that m…
Proenzyme Structure and Activation of Astacin Metallopeptidase
2010
Proteolysis is regulated by inactive (latent) zymogens, with a prosegment preventing access of substrates to the active-site cleft of the enzyme. How latency is maintained often depends on the catalytic mechanism of the protease. For example, in several families of the metzincin metallopeptidases, a >cysteine switch> mechanism involves a conserved prosegment motif with a cysteine residue that coordinates the catalytic zinc ion. Another family of metzincins, the astacins, do not possess a cysteine switch, so latency is maintained by other means. We have solved the high resolution crystal structure of proastacin from the European crayfish, Astacus astacus. Its prosegment is the shortest struc…
Characterization of two Lactococcus lactis zinc membrane proteins, Llmg_0524 and Llmg_0526, and role of Llmg_0524 in cell wall integrity
2015
Background Due to its extraordinary chemical properties, the cysteine amino acid residue is often involved in protein folding, electron driving, sensing stress, and binding metals such as iron or zinc. Lactococcus lactis, a Gram-positive bacterium, houses around one hundred cysteine-rich proteins (with the CX2C motif) in the cytoplasm, but only a few in the membrane. Results In order to understand the role played by this motif we focused our work on two membrane proteins of unknown function: Llmg_0524 and Llmg_0526. Each of these proteins has two CX2C motifs separated by ten amino-acid residues (CX2CX10CX2C). Together with a short intervening gene (llmg_0525), the genes of these two protein…
Nitric oxide inhibits the ATPase activity of the chaperone-like AAA+ ATPase CDC48, a target for S-nitrosylation in cryptogein signalling in tobacco c…
2012
NO has important physiological functions in plants, including the adaptative response to pathogen attack. We previously demonstrated that cryptogein, an elicitor of defence reaction produced by the oomycete Phytophthora cryptogea , triggers NO synthesis in tobacco. To decipher the role of NO in tobacco cells elicited by cryptogein, in the present study we performed a proteomic approach in order to identify proteins undergoing S-nitrosylation. We provided evidence that cryptogein induced the S-nitrosylation of several proteins and identified 11 candidates, including CDC48 (cell division cycle 48), a member of the AAA+ ATPase (ATPase associated with various cellular activities) family. In vit…
The use of low-resolution phasing followed by phase extension from 7.6 to 2.5 Å resolution with noncrystallographic symmetry to solve the structure o…
2011
P2, the major capsid protein of bacteriophage PM2, adopts the double β-barrel fold characteristic of the PRD1-adenoviral lineage. The 2.5 Å resolution X-ray data obtained by analysis of the two major lattices of a multiple crystal of P2 were phased by molecular replacement, using as a search model structure factors to 7.6 Å resolution obtained from electron density cut from the map of the entire PM2 virion. Phase extension to 2.5 Å resolution used solely sixfold cycling averaging and solvent flattening. This represents an atypical example of an oligomeric protein for which the structure has been determined at high resolution by bootstrapping from low-resolution initial phases.
Full Domain Closure of the Ligand-binding Core of the Ionotropic Glutamate Receptor iGluR5 Induced by the High Affinity Agonist Dysiherbaine and the …
2009
The prevailing structural model for ligand activation of ionotropic glutamate receptors posits that agonist efficacy arises from the stability and magnitude of induced domain closure in the ligand-binding core structure. Here we describe an exception to the correlation between ligand efficacy and domain closure. A weakly efficacious partial agonist of very low potency for homomeric iGluR5 kainate receptors, 8,9-dideoxyneodysiherbaine (MSVIII-19), induced a fully closed iGluR5 ligand-binding core. The degree of relative domain closure, approximately 30 degrees , was similar to that we resolved with the structurally related high affinity agonist dysiherbaine and to that of l-glutamate. The ph…
Identification of residues in the putative 5th helical region of human interleukin-6, important for activation of the IL-6 signal transducer, gp130
1996
AbstractWe have previously shown that L58 in the putative 5th helical region of human interleukin-6 (IL-6) is important for activation of the IL-6 signal transducer gp130 [de Hon et al. (1995) FEBS Lett. 369, 187–191]. To further explore the importance of individual residues in this region for gp130 activation we have now combined Ala substitutions of residues E52, S53, S54, K55, E56, L58 and E60 with other substitutions in IL-6, known to affect gp130 activation (Q160E and T163P). The combination mutant protein with L58A completely lost the capacity to induce the proliferation of XG-1 myeloma cells, and could effectively antagonize wild type IL-6 activity on these cells. Moreover, the data …
Charge Pair Interactions in Transmembrane Helices and Turn Propensity of the Connecting Sequence Promote Helical Hairpin Insertion
2013
alpha-Helical hairpins, consisting of a pair of closely spaced transmembrane (TM) helices that are connected by a short interfacial turn, are the simplest structural motifs found in multi-spanning membrane proteins. In naturally occurring hairpins, the presence of polar residues is common and predicted to complicate membrane insertion. We postulate that the pre-packing process offsets any energetic cost of allocating polar and charged residues within the hydrophobic environment of biological membranes. Consistent with this idea, we provide here experimental evidence demonstrating that helical hairpin insertion into biological membranes can be driven by electrostatic interactions between clo…