Peculiar Folding Research Articles

A widespread new genus of Baetidae (Baetidae, Ephemeroptera) from Southeast Asia.

A reinvestigation of type and other material of Baetisjavanicus Ulmer, 1913 and Baetissabahensis Müller-Liebenau, 1984, together with new material from Southeast Asia revealed a new genus, Branchiobaetis gen. nov. The above species are formally assigned to the new genus Branchiobaetis gen. nov. It is characterized by the presence of accessory gills ventrally near fore coxa and at the base of maxillae, a peculiar folding of the gonostyli developing under the cuticle of last instar male larvae, together with a unique combination of other larval characters. Besides the two formerly described species, five new species are identified using a combination of morphology and molecular characters (COI, Kimura 2-parameter distances), four species from Sumatra and one from the Philippines. They are described and illustrated at the larval stage. Additionally, a complementary description of larva and adult stages of the generic type species B.javanicus comb. nov. as well as the first description of the eggs are provided. Furthermore, new reports of B.javanicus comb. nov. and B.sabahensis comb. nov. are indicated. The distribution of Branchiobaetis gen. nov. includes the Indonesian Sunda Islands, Borneo, and the Philippines. A key to the larval stage of all species is provided.

A systematic structural comparison of all solved small proteins deposited in PDB. The effect of disulfide bonds in protein fold

Defensins are small proteins, usually ranging from 3 to 6 kDa, amphipathic, disulfide-rich, and with a small or even absent hydrophobic core. Since a hydrophobic core is generally found in globular proteins that fold in an aqueous solvent, the peculiar fold of defensins can challenge tertiary protein structure predictors. We performed a Protein Data Bank survey of small proteins (3–6 kDa) to understand the similarities of defensins with other small disulfide-rich proteins. We found no differences when we compared defensins with non-defensins regarding the proportion of apolar, polar and charged residues and their exposure to the solvent. Then we divided all small proteins (3–6 kDa) in the Protein Data Bank into two groups, one group with at least one disulfide bond (bonded, defensins included) and another group without any disulfide bond (unbonded). The group of bonded proteins contained apolar residues more exposed to the solvent than the unbonded group. The ab initio algorithm for tertiary protein structure prediction Robetta was more accurate at predicting unbonded than bonded proteins. On the other hand, the trRosetta algorithm, which uses artificial intelligence, improved the prediction of most bonded proteins, while for the unbonded group no improvement was obtained. Our work highlights one more layer of complexity for the prediction of protein tertiary structure: The ability of small disulfide-rich proteins to fold even with a poorly hydrophobic core.

The kinetics of folding of the NSH2 domain from p85

SH2 domains are protein domains that mediate protein-protein interaction through the recognition and binding of specific sequences containing phosphorylated tyrosines. The p85 protein is the regulatory subunit of the heterodimeric enzyme PI3K, an important enzyme involved in several molecular pathways. In this work we characterize the folding kinetics of the NSH2 domain of p85. Our data clearly reveal peculiar folding kinetics, characterized by an apparent mismatch between the observed folding and unfolding kinetics. Taking advantage of double mixing stopped flow experiments and site directed mutagenesis we demonstrate that such behavior is due to the cis/trans isomerization of the peptide bond between D73 and P74, being in a cis conformation in the native protein. Our data are discussed in comparison with previous works on the folding of other SH2 domains.

Antennal fine morphology of the threatened beetle Osmoderma eremita (Coleoptera: Scarabaeidae), revealed by scanning electron microscopy

The aim of this study was to characterize the antennal morphology of Osmoderma eremita, a threatened scarab beetle inhabiting tree hollows. O. eremita males produce a sex pheromone, (R)-(+)-γ-decalactone, responsible mainly for the attraction of females but also other males. Gross and fine morphology of microstructures including sensilla, microsculpture and pores were analyzed using Scanning Electron Microscopy. The antenna of O. eremita showed the typical lamellicorn shape of scarab beetles, with a basal scape, a pedicel, a funicle composed of five antennomeres and a club composed of three lamellae. Six different subtypes of sensilla chaetica (Ch.1 - 6), Böhm sensilla (Bo), one subtype of sensilla basiconica (Ba.1), two subtypes of sensilla coeloconica (Co.1 - 2), two subtypes of sensilla placodea (Pl.1 - 2), pores and peculiar folds were described. The two sexes did not show any significant differences in the occurrence and number of the sensilla placodea, known to be responsible for the pheromone reception. Instead, some sexual differences were found on the occurrence and topology of three different microstructures: (1) one subtype of sensillum chaeticum (Ch.2) occurring on the pedicel only in males; (2) a characteristic pore occurring on the funicle only in males; (3) a peculiar fold occurring on different antennomeres of the funicle in the two sexes, on the fourth in males and on the fifth in females. A comparison between sensilla of O. eremita and those of other Scarabaeoidea is provided.

From coherent shocklets to giant collective incoherent shock waves in nonlocal turbulent flows.

Understanding turbulent flows arising from random dispersive waves that interact strongly through nonlinearities is a challenging issue in physics. Here we report the observation of a characteristic transition: strengthening the nonlocal character of the nonlinear response drives the system from a fully turbulent regime, featuring a sea of coherent small-scale dispersive shock waves (shocklets) towards the unexpected emergence of a giant collective incoherent shock wave. The front of such global incoherent shock carries most of the stochastic fluctuations and is responsible for a peculiar folding of the local spectrum. Nonlinear optics experiments performed in a solution of graphene nano-flakes clearly highlight this remarkable transition. Our observations shed new light on the role of long-range interactions in strongly nonlinear wave systems operating far from thermodynamic equilibrium, which reveals analogies with, for example, gravitational systems, and establishes a new scenario that can be common to many turbulent flows in photonic quantum fluids, hydrodynamics and Bose–Einstein condensates.

Structural and Functional Insights into Peptidoglycan Access for the Lytic Amidase LytA of Streptococcus pneumoniae

ABSTRACTThe cytosolic N-acetylmuramoyl-l-alanine amidase LytA protein of Streptococcus pneumoniae, which is released by bacterial lysis, associates with the cell wall via its choline-binding motif. During exponential growth, LytA accesses its peptidoglycan substrate to cause lysis only when nascent peptidoglycan synthesis is stalled by nutrient starvation or β-lactam antibiotics. Here we present three-dimensional structures of LytA and establish the requirements for substrate binding and catalytic activity. The solution structure of the full-length LytA dimer reveals a peculiar fold, with the choline-binding domains forming a rigid V-shaped scaffold and the relatively more flexible amidase domains attached in a trans position. The 1.05-Å crystal structure of the amidase domain reveals a prominent Y-shaped binding crevice composed of three contiguous subregions, with a zinc-containing active site localized at the bottom of the branch point. Site-directed mutagenesis was employed to identify catalytic residues and to investigate the relative impact of potential substrate-interacting residues lining the binding crevice for the lytic activity of LytA. In vitro activity assays using defined muropeptide substrates reveal that LytA utilizes a large substrate recognition interface and requires large muropeptide substrates with several connected saccharides that interact with all subregions of the binding crevice for catalysis. We hypothesize that the substrate requirements restrict LytA to the sites on the cell wall where nascent peptidoglycan synthesis occurs.

Self-Organization of Mixtures of Fluorocarbon and Hydrocarbon Amphiphilic Thiolates on the Surface of Gold Nanoparticles

Self-assembled monolayers composed of a mixture of thiolate molecules, featuring hydrocarbon or perfluorocarbon chains (H- and F-chains) terminating with a short poly(oxoethylene) (PEG) moiety, are the most extreme example of surfactant immiscibility on gold nanoparticles reported so far. The phase segregation between H-chains and F-chains and the consequent, peculiar folding of PEG chains are responsible for the increased affinity of a selected radical probe for the fluorinated region, which increases as the size of the fluorinated domains decrease, independently of the shape of such domains. This feature has been revealed by ESR measurements and an in silico innovative multiscale molecular simulations approach in explicit water. Our results reveal an underlying mechanism of a transmission of the organization of the monolayer from the inner region close to the gold surface toward the external hydrophilic PEG region. Moreover, this study definitively proves that a mixed monolayer is a complex system with properties markedly different from those characterizing the parent homoligand monolayers.

Molecular Origin of Piezo- and Pyroelectric Properties in Collagen Investigated by Molecular Dynamics Simulations

Molecular dynamics simulations were used to study the effect of mechanical and thermal stimuli on the electrostatic properties of collagen model helices. Our model sequences were based on glycine proline and hydroxyproline amino acids. We find that longitudinal mechanical strain induces significant variation of the polarization of the collagen fibril. Such a phenomenon is determined by reorientation of the backbone polar groups, which are free to respond to the mechanical solicitation. This non-negligible effect is facilitated by the peculiar folding structure of the collagen helix, which is characterized by the absence of an extended hydrogen-bond network. The stretching/compression of the helix requires a concomitant winding/unwinding motion of the global structure; therefore, the shear components of the stress tensor are the components that most effectively induce structural modification associated to the piezoelectric response. The present calculations also report a pyroelectric response to thermal activation. Model calculations indicate that the pyroelectric effect is dominated by secondary components associated with the piezoelectric tensor.

Near Native-State Conformational Landscape of Psychrophilic and Mesophilic Enzymes: Probing the Folding Funnel Model

In recent years, increased interest has been directed to the study of enzyme adaptation to low temperatures. In particular, a peculiar folding funnel model was proposed for the free energy landscape of a psychrophilic alpha-amylase and other cold-adapted enzymes. In the present contribution, the comparison between the near native-state dynamics and conformational landscape in the essential subspace of different cold-adapted enzymes with their mesophilic counterparts, as obtained by more than 0.1 micros molecular dynamics simulations at different temperatures, allows the folding funnel model to be probed. Common characteristics were highlighted in the near native-state dynamics of psychrophilic enzymes belonging to different enzymatic families when compared to the mesophilic counterparts. According to the model, a cold-adapted enzyme in its native-state consists of a large population of conformations which can easily interconvert and result in high structural flexibility.

Structural Features of Distinctin Affecting Peptide Biological and Biochemical Properties

The antimicrobial peptide distinctin consists of two peptide chains linked by a disulfide bridge; it presents a peculiar fold in water resulting from noncovalent dimerization of two heterodimeric molecules. To investigate the contribution of each peptide chain and the S-S bond to distinctin biochemical properties, different monomeric and homodimeric peptide analogues were synthesized and comparatively evaluated with respect to the native molecule. Our experiments demonstrate that the simultaneous occurrence of both peptide chains and the disulfide bond is essential for the formation of the quaternary structure of distinctin in aqueous media, able to resist protease action. In contrast, distinctin and monomeric and homodimeric analogues exhibited comparable antimicrobial activities, suggesting only a partial contribution of the S-S bond to peptide killing effectiveness. Relative bactericidal properties paralleled liposome permeabilization results, definitively demonstrating that microbial membranes are the main target of distinctin activity. Various biophysical experiments performed in membrane-mimicking media, before and after peptide addition, provided information about peptide secondary structure, lipid bilayer organization, and lipid-peptide orientation with respect to membrane surface. These data were instrumental in the generation of putative models of peptide-lipid supramolecular pore complexes.

Investigation into the Formation of Supramolecular Compounds from Mixed As/S-Ligand Complexes [(Cp*Mo)2As2S3] (Cp* = C5Me5) and Copper Halides

The coordination behavior of [(Cp*Mo)2As2S3] (3) (Cp* = C5Me5) toward Cu(I) halides was investigated. One dimensional polymers of the general formula [(Cp*Mo)2As2S3(CuHal)2]n (Hal = Cl, 4; Br, 5) and an oligomer of composition [{(Cp*Mo)2As2S3}3(CuI)7] (6) formed upon the reaction of 3 with the corresponding copper halide. All of the compounds were characterized by ESI-MS, elemental analysis, and single-crystal X-ray crystallography. The solid-state structures of 4 and 5 are isostructural and contain 1D S-shaped chains. This peculiar folding is achieved by alternating planar and folded Cu2Hal2 rings linked together by the central monosulfide bridge of the middle deck of the organometallic unit. The structure of 6 is characterized by a novel [CuI]7 aggregate, which forms a very flat Cu6I3S3 bowl along with three integrated peripheral [(Cp*Mo)2As2S3] building blocks. In contrast to earlier findings, the middle deck of the organometallic units consists in all structures of two trapezoidal AsS dumbbells and one monosulfide ligand.

A Core Mutation Affecting the Folding Properties of a Soluble Domain of the ATPase Protein CopA from Bacillus subtilis

The two N-terminal domains of the P-type copper ATPase, CopAa and CopAb, from Bacillus subtilis differ in their folding capabilities in vitro. Whereas CopAb has the typical βαββαβ structure and is a rigid protein, CopAa is found to be largely unfolded. A sequence analysis of the two and of orthologue homologous proteins indicates that Ser46 in CopAa may destabilise the hydrophobic core, as also confirmed through a bioinformatic energy study. CopAb has a Val in the corresponding position. The S46V and S46A mutants are found to be folded, although the latter displays multiple conformations. S46VCopAa, in both apo and copper(I) loaded forms, has very similar structural and dynamic properties with respect to CopAb, besides a different length of strand β2 and β4. It is intriguing that the oxygen of Thr16 is found close, though at longer than bonding distance, to copper in both domains, as it also occurs in a human orthologue domain. This study contributes to understanding the behaviour of proteins that do not properly fold in vitro. A possible biological significance of the peculiar folding behaviour of this domain is discussed.

Loss of apoB-100 secondary structure and conformation in hydroperoxide rich, electronegative LDL −

A subpopulation of low-density lipoproteins (LDL) is present in human plasma that contains lipid hydroperoxides and is more negatively charged (LDL −) than normal native LDL. By circular dichroism and tryptophan lifetime measurements we found that apoB-100 secondary structure is markedly decreased and its conformation is severely altered in LDL −. The low tryptophan fluorescence intensity confirms the oxidative degradation of the lipoprotein, and the very long lifetime value of one of its decay components indicates a low polarity environment for the remaining unbleached residues. Either a peculiar folding or, most likely, a sinking of the apoB-100 into the lipid core can account for the observed long lifetime component. Oxidation in vitro produces a similar unfolding of the apolipoprotein but the lifetime of tryptophan fluorescence is shifted to lower values, indicating that the denatured apoprotein remains at the hydrophilic surface of the lipoprotein particle. A disordering and an increased polarity of the LDL − surface lipids was demonstrated by measuring the generalized polarization of 2-dimethylamino-6-lauroylnaphthalene (Laurdan). The looser monolayer packing apparently favors the new conformation of apoB-100 and its sinking into a more hydrophobic environment, possibly accounting for it reduced receptor binding properties.

SEISMIC STUDIES OF THE UPPER MANTLE BENEATH THE ARC-JUNCTION AT HOKKAIDO

Distribution of intermediate and deep earthquake hypocenters beneath the Hokkaido corner, one of the notable arc-junctions in Japan, is investigated. A specially designed projection of the hypocenters is made to demonstrate the configuration of the seismic zone beneath the arc-junction. The configuration is characterized by a peculiar folding in the depth range between 80 and 150km, which seems to be caused by plastic deformation of the descending lithosphere.Attenuation of seismic waves of local earthquakes is also studied. Q values for S waves fall in the range between 50 and 200 in the upper mantle beneath Hokkaido. The distribution of Q values shows that the high attenuation zones correspond to the areas of high heat flow.

CUTIS VERTICIS GYRATA

Since Unna, 1 in 1907, introduced the name of cutis verticis gyrata to indicate that peculiar fold and furrow formation seen in certain scalps, there have been one hundred and fifty-eight cases of the condition reported by eighty-seven authors. Jadassohn, 2 a year earlier, presented a case at the Ninth Congress of Dermatologists in Bern, and he is credited with being the first to bring this disease to the attention of dermatologists. Neuropsychiatrists, however, were acquainted with the condition at an earlier date. In 1893, McDowall, 3 for instance, described, with illustrations, a case in an epileptic microcephalic idiot, and Cowan 4 in the same year recorded two similarly abnormal scalps in idiots. A perusal of the earlier case reports discloses a great diversity of opinion regarding the etiology of this disease. Those authors who believe it to be due wholly or in part to inflammatory changes include von Veress,