Search results for "DOMAINS"
showing 10 items of 269 documents
Oligomerization and hemolytic properties of the C-terminal domain of pyolysin, a cholesterol-dependent cytolysin
2013
Pyolysin (PLO) belongs to the homologous family of the cholesterol- dependent cytolysins (CDCs), which bind to cell membranes containing cholesterol to form oligomeric pores of large size. The CDC monomer structure consists of 4 domains. Among these, the C-terminal domain 4 has been implicated in membrane binding of the monomer, while the subsequent processes of oligomerization and membrane insertion have primarily been assigned to other domains of the molecule. Recombinantly expressed or proteolytic fragments that span domain 4 of the CDCs streptolysin O and perfringolysin O bind to membranes but fail to oligomerize, and they inhibit the activity of the respective wild-type toxins. We repo…
Evidence that clustered phosphocholine head groups serve as sites for binding and assembly of an oligomeric protein pore.
2006
High susceptibility of rabbit erythrocytes toward the pore-forming action of staphylococcal alpha-toxin correlates with the presence of saturable, high affinity binding sites. All efforts to identify a protein or glycolipid receptor have failed, and the fact that liposomes composed solely of phosphatidylcholine are efficiently permeabilized adds to the enigma. A novel concept is advanced here to explain the puzzle. We propose that low affinity binding moieties can assume the role of high affinity binding sites due to their spatial arrangement in the membrane. Evidence is presented that phosphocholine head groups of sphingomyelin, clustered in sphingomyelin-cholesterol microdomains, serve th…
The pioneering role of PRDM9 indel mutations in tarsier evolution
2016
PRDM9 is currently the sole speciation gene found in vertebrates causing hybrid sterility probably due to incompatible alleles. Its role in defining the double strand break loci during the meiotic prophase I is crucial for proper chromosome segregation. Therefore, the rapid turnover of the loci determining zinc finger array seems to be causative for incompatibilities. We here investigated the zinc finger domain-containing exon of PRDM9 in 23 tarsiers. Tarsiers, the most basal extant haplorhine primates, exhibit two frameshifting indels at the 5'-end of the array. The first mutation event interrupts the reading frame and function while the second compensates both. The fixation of this allele…
Extracellular Hsp70 Enhances Mesoangioblast Migration via an Autocrine Signaling Pathway
2016
Mouse mesoangioblasts are vessel-associated progenitor stem cells endowed with the ability of multipotent mesoderm differentiation. Therefore, they represent a promising tool in the regeneration of injured tissues. Several studies have demonstrated that homing of mesoangioblasts into blood and injured tissues are mainly controlled by cytokines/chemokines and other inflammatory factors. However, little is known about the molecular mechanisms regulating their ability to traverse the extracellular matrix (ECM). Here, we demonstrate that membrane vesicles released by mesoangioblasts contain Hsp70, and that the released Hsp70 is able to interact by an autocrine mechanism with Toll-like receptor …
Free boundary methods and non-scattering phenomena
2021
We study a question arising in inverse scattering theory: given a penetrable obstacle, does there exist an incident wave that does not scatter? We show that every penetrable obstacle with real-analytic boundary admits such an incident wave. At zero frequency, we use quadrature domains to show that there are also obstacles with inward cusps having this property. In the converse direction, under a nonvanishing condition for the incident wave, we show that there is a dichotomy for boundary points of any penetrable obstacle having this property: either the boundary is regular, or the complement of the obstacle has to be very thin near the point. These facts are proved by invoking results from t…
Antidepressants and Antipsychotic Drugs Colocalize with 5-HT(3) Receptors in Raft-Like Domains
2005
Despite different chemical structure and pharmacodynamic signaling pathways, a variety of antidepressants and antipsychotics inhibit ion fluxes through 5-HT3receptors in a noncompetitive manner with the exception of the known competitive antagonists mirtazapine and clozapine. To further investigate the mechanisms underlying the noncompetitive inhibition of the serotonin-evoked cation current, we quantified the concentrations of different types of antidepressants and antipsychotics in fractions of sucrose flotation gradients isolated from HEK293 (human embryonic kidney 293) cells stably transfected with the 5-HT3Areceptor and of N1E-115 neuroblastoma cells in relation to the localization of …
Accessible parts of boundary for simply connected domains
2018
For a bounded simply connected domain $\Omega\subset\mathbb{R}^2$, any point $z\in\Omega$ and any $0<\alpha<1$, we give a lower bound for the $\alpha$-dimensional Hausdorff content of the set of points in the boundary of $\Omega$ which can be joined to $z$ by a John curve with a suitable John constant depending only on $\alpha$, in terms of the distance of $z$ to $\partial\Omega$. In fact this set in the boundary contains the intersection $\partial\Omega_z\cap\partial\Omega$ of the boundary of a John sub-domain $\Omega_z$ of $\Omega$, centered at $z$, with the boundary of $\Omega$. This may be understood as a quantitative version of a result of Makarov. This estimate is then applied to obta…
Direct experimental observation of mesoscopic fluorous domains in fluorinated room temperature ionic liquids
2017
Fluorinated room temperature ionic liquids (FRTILs) represent a class of solvent media that are attracting great attention due to their IL-specific properties as well as features stemming from their fluorous nature. Medium-to-long fluorous tails constitute a well-defined apolar moiety in the otherwise polar environment. Similarly to the case of alkyl tails, such chains are expected to result in the formation of self-assembled fluorous domains. So far, however, no direct experimental observation has been made of the existence of such structural heterogeneities on the nm scale. We report here the first experimental evidence of the existence of mesoscopic spatial segregation of fluorinated dom…
Comparative analysis of two paradigm bacteriophytochromes reveals opposite functionalities in two-component signaling
2021
Bacterial phytochrome photoreceptors usually belong to two-component signaling systems which transmit environmental stimuli to a response regulator through a histidine kinase domain. Phytochromes switch between red light-absorbing and far-red light-absorbing states. Despite exhibiting extensive structural responses during this transition, the model bacteriophytochrome from Deinococcus radiodurans (DrBphP) lacks detectable kinase activity. Here, we resolve this long-standing conundrum by comparatively analyzing the interactions and output activities of DrBphP and a bacteriophytochrome from Agrobacterium fabrum (Agp1). Whereas Agp1 acts as a conventional histidine kinase, we identify DrBphP a…
N- and O-methylation of sphingomyelin markedly affects its membrane properties and interactions with cholesterol
2011
We have prepared palmitoyl sphingomyelin (PSM) analogs in which either the 2-NH was methylated to NMe, the 3-OH was methylated to OMe, or both were methylated simultaneously. The aim of the study was to determine how such modifications in the membrane interfacial region of the molecules affected interlipid interactions in bilayer membranes. Measuring DPH anisotropy in vesicle membranes prepared from the SM analogs, we observed that methylation decreased gel-phase stability and increased fluid phase disorder, when compared to PSM. Methylation of the 2-NH had the largest effect on gel-phase instability (T(m), was lowered by similar to 7 degrees C). Atomistic molecular dynamics simulations sho…