共查询到20条相似文献,搜索用时 15 毫秒
1.
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Liu Z Dai J Chen Z Hu W Xiao Y Liang S 《Cellular and molecular life sciences : CMLS》2003,60(5):972-978
A neurotoxin, named hainantoxin-IV, was purified from the venom of the spider Selenocosmia hainana. The amino acid sequence was determined by Edman degradation, revealing it to be a 35-residue polypeptide amidated at its C terminal and including three disulfide bridges: Cys2-Cys17, Cys9-Cys24, and Cys16-Cys31 assigned by partial reduction and sequence analysis. Hainantoxin-IV shares 80% sequence identity with huwentoxin-IV from the spider S. huwena, a potent antagonist that acts at site 1 on tetrodotoxin-sensitive (TTX-S) sodium channels, suggesting that hainantoxin-IV adopts an inhibitor cystine knot structural motif like huwentoin-IV. Under whole-cell voltage-clamp conditions, this toxin has no effect on tetrodotoxin-resistant voltage-gated sodium channels in adult rat dorsal root ganglion neurons, while it blocks TTX-S sodium channels in a manner similar to huwentoxin-IV, and the actions of both toxins on sodium currents are very similar to that of tetrodotoxin. Thus, they define a new family of spider toxins affecting sodium channels. 相似文献
3.
Advances in mass spectrometry and peptide biochemistry coupled to modern methods in electrophysiology have permitted the isolation and identification of numerous novel peptide toxins from animal venoms in recent years. These advances have also opened up the field of spider venom research, previously unexplored due to methodological limitations. Many peptide toxins from spider venoms share structural features, amino acid composition and consensus sequences that allow them to interact with related classes of cellular receptors. They have become increasingly useful agents for the study of voltage-sensitive and ligand-gated ion channels and the discrimination of their cellular subtypes. Spider peptide toxins have also been recognized as useful agents for their antimicrobial properties and the study of pore formation in cell membranes. Spider peptide toxins with nanomolar affinities for their receptors are thus promising pharmacological tools for understanding the physiological role of ion channels and as leads for the development of novel therapeutic agents and strategies for ion channel-related diseases. Their high insecticidal potency can also make them useful probes for the discovery of novel insecticide targets in the insect nervous system or for the development of genetically engineered microbial pesticides.Received 19 March 2003; received after revision 9 May 2003; accepted 16 May 2003 相似文献
4.
Ligand recognition by the I domain-containing integrins 总被引:11,自引:0,他引:11
Seven of the integrin α subunits described to date, α 1 , α 2 , α L , α X , α d , α M and α E , contain a highly conserved I (or A) domain of approximately 200 amino acid residues inserted near the amino-terminus of the subunit. As the result of a variety of independent experimental approaches, a large body of data has recently accumulated that indicates that the I domains are independent, autonomously folding domains capable of directly binding ligands that play a necessary and important role in ligand binding by the intact integrins. Recent crystallographic studies have elucidated the structures of recombinant α M and α L I domains and also delineated a novel divalent cation-binding motif within the I domains (metal ion-dependent adhesion site, MIDAS) that appears to mediate the divalent cation binding of the I domains and the I domain-containing integrins to their ligands. 相似文献
5.
J. van Marle T. Piek H. Karst A. Lind J. van Weeren-Kramer 《Cellular and molecular life sciences : CMLS》1989,45(2):155-156
In contrast to the reported effects of polyamines on the high affinity neurotransmitter uptake, two polyamine-like spider toxins significantly increase the high affinity uptake of glutamate as demonstrated with high resolution autoradiography. The effects of both spider toxins were compared to those of a polyamine toxin from the waspPhilanthus triangulum, which is known to inhibit the high affinity glutamate uptake. 相似文献
6.
Tommy Baumann Urs Kämpfer Stefan Schürch Johann Schaller Carlo Largiadèr Wolfgang Nentwig Lucia Kuhn-Nentwig 《Cellular and molecular life sciences : CMLS》2010,67(16):2787-2798
Three novel glycine-rich peptides, named ctenidin 1–3, with activity against the Gram-negative bacterium E. coli, were isolated and characterized from hemocytes of the spider Cupiennius salei. Ctenidins have a high glycine content (>70%), similarly to other glycine-rich peptides, the acanthoscurrins, from another spider, Acanthoscurria gomesiana. A combination of mass spectrometry, Edman degradation, and cDNA cloning revealed the presence of three isoforms of ctenidin, at least two of them originating from simple, intronless genes. The full-length sequences of the ctenidins consist of a 19 amino acid residues signal peptide followed by the mature peptides of 109, 119, or 120 amino acid residues. The mature peptides are post-translationally modified by the cleavage of one or two C-terminal cationic amino acid residue(s) and amidation of the newly created mature C-terminus. Tissue expression analysis revealed that ctenidins are constitutively expressed in hemocytes and to a small extent also in the subesophageal nerve mass. 相似文献
7.
The venoms of predatory cone snails harbor a rich repertoire of peptide toxins that are valuable research tools, but recently
have also proven to be useful drugs. Among the conotoxins with several disulfide bridges, the O-superfamily toxins are characterized
by a conserved cysteine knot pattern: C-C-CC-C-C. While ω-conotoxins and κ-conotoxins block Ca2+ and K+ channels, respectively, the closely related δ- and μO-conotoxins affect voltage-gated Na+ channels (Nav channels). δ-conotoxins mainly remove the fast inactivation of Nav channels and, thus, functionally resemble long-chain scorpion α-toxins. μO-conotoxins are functionally similar to μ-conotoxins,
since they inhibit the ion flow through Nav channels. Recent results from functional and structural assays have gained insight into the underlying molecular mechanisms.
Both types of toxins are voltage-sensor toxins interfering with the voltage-sensor elements of Nav channels.
Received 27 December 2006; received after revision 30 January 2007; accepted 19 February 2007 相似文献
8.
M. Capdevila N. Cols N. Romero-Isart R. Gonzàlez-Duarte S. Atrian P. Gonzàlez-Duarte 《Cellular and molecular life sciences : CMLS》1997,53(8):681-688
Genetic engineering, coupled with spectro scopic analyses, has enabled the metal binding proper ties of the α and β subunits of mouse metallothionein 1 (MT) to be characterized. A heterologous expression system in E.coli has led to high yields of their pure zinc-complexed forms. The cadmium(II) binding properties of recombinant Zn4-αMT and Zn3-βMT have been studied by electronic absorption and circular dichroism. The former binds Cd(II) identically to α fragments obtained from mammalian organs, showing that the recombinant polypeptide behaves like the na tive protein. Titration
of Zn3-βMT with CdCl2 results in the formation of Cd3-βMT. The addition of excess Cd(II) leads to Cd4-βMT which, with the extra loading of Cd(II), unravels to give rise isodichroically to Cd9-βMT. The effect of cadmium-displaced Zn(II) ions and excess Cd(II) above the full metal occupancy of three has been studied
using Chelex-100. The Cd3-βMT species is stable in the presence of this strong metal-chelating agent.
Received 20 May 1997; received after revision 7 July 1997; accepted 9 July 1997 相似文献
9.
Cellular pathology induced by snake venom phospholipase A2 myotoxins and neurotoxins: common aspects of their mechanisms of action 总被引:3,自引:0,他引:3
Montecucco C Gutiérrez JM Lomonte B 《Cellular and molecular life sciences : CMLS》2008,65(18):2897-2912
A large variety of snake toxins evolved from PLA2 digestive enzymes through a process of ‘accelerated evolution’. These toxins have different tissue targets, membrane receptors
and mechanisms of alteration of the cell plasma membrane. Two of the most commonly induced effects by venom PLA2s are neurotoxicity and myotoxicity. Here, we will discuss how these snake toxins achieve a similar cellular lesion, which
is evolutionarily highly conserved, despite the differences listed above. They cause an initial plasma membrane perturbation
which promotes a large increase of the cytosolic Ca2+ concentration leading to cell degeneration, following modes that we discuss in detail for muscle cells and for the neuromuscular
junction. The different systemic pathophysiological consequences caused by these toxins are not due to different mechanisms
of cell toxicity, but to the intrinsic anatomical and physiological properties of the targeted tissues and cells.
Received 05 March 2008; received after revision 08 April 2008; accepted 29 April 2008 相似文献
10.
Pepsinogens, progastricsins, and prochymosins: structure, function, evolution, and development 总被引:12,自引:0,他引:12
Kageyama T 《Cellular and molecular life sciences : CMLS》2002,59(2):288-306
Five types of zymogens of pepsins, gastric digestive proteinases, are known: pepsinogens A, B, and F, progastricsin, and
prochymosin. The amino acid and/or nucleotide sequences of more than 50 pepsinogens other than pepsinogen B have been determined
to date. Phylogenetic analyses based on these sequences indicate that progastricsin diverged first followed by prochymosin,
and that pepsinogens A and F are most closely related. Tertiary structures, clarified by X-ray crystallography, are commonly
bilobal with a large active-site cleft between the lobes. Two aspartates in the center of the cleft, Asp32 and Asp215, function
as catalytic residues, and thus pepsinogens are classified as aspartic proteinases. Conversion of pepsinogens to pepsins proceeds
autocatalytically at acidic pH by two different pathways, a one-step pathway to release the intact activation segment directly,
and a stepwise pathway through a pseudopepsin(s). The active-site cleft is large enough to accommodate at least seven residues
of a substrate, thus forming S4 through S3′ subsites. Hydrophobic and aromatic amino acids are preferred at the P1 and P1′ positions. Interactions at additional subsites are important in some cases, for example with cleavage of κ-casein by chymosin. Two potent naturally occurring inhibitors are known: pepstatin, a pentapeptide from Streptomyces, and a unique proteinous inhibitor from Ascaris. Pepsinogen genes comprise nine exons and may be multiple, especially for pepsinogen A. The latter and progastricsin predominate
in adult animals, while pepsinogen F and prochymosin are the main forms in the fetus/infant. The switching of gene expression
from fetal/infant to adult-type pepsinogens during postnatal development is noteworthy, being regulated by several factors,
including steroid hormones.
Received 25 May 2001; received after revision 27 August 2001; accepted 30 August 2001 相似文献
11.
A. Zhang T. P.-O. Cheng X. Y. Wu B. T. Altura B. M. Altura 《Cellular and molecular life sciences : CMLS》1997,53(1):69-72
Effects of extracellular magnesium ions ([Mg2+]o ) on intracellular free Mg2+ ([Mg2+]i ) and its subcellular distribution in single fission yeast cells, Schizosaccharomyces pombe, were studied with digital-imaging microscopy and an Mg2+ fluorescent probe (mag-fura-2). Using 0.44 mM [Mg2+]o , [Mg2+]i in yeast cells was 0.91±0.08 mM. Elevation of [Mg2+]o to 1.97 mM induced rapid (within 5 min) increments in [Mg2+]i (2.18±0.11 mM). Lowering [Mg2+]o to 0.06 mM, however, exerted no significant effects on [Mg2+]i (0.93±0.14 mM), at least for periods of up to 30 min. Irrespective of the [Mg2+]o used, the subcellular distribution of [Mg2+]i remained hetero
geneous, i.e. where the sub-plasma membrane region >cytoplasm >nucleus. [Mg2+] in all three subcellular compartments increased significantly, two- to threefold, concomitant with [Mg2+]i when placed in 1.97 mM [Mg2+]o . We conclude that [Mg2+]i in fission yeast is maintained at a physiologic level when [Mg2+]o is low, but intracellular free Mg2+ rapidly rises when [Mg2+]o is elevated. Like most eukaryotic cells, yeast may have a Mg2+ transport system(s) which functions to maintain gradients of Mg2+ from the outside to inside the cell and among its subcellular compartments.
Received 18 April 1996; received after revision 4 July 1996; accepted 26 July 1996 相似文献
12.
Sporulation and δ-endotoxin synthesis by Bacillus thuringiensis 总被引:4,自引:0,他引:4
Aronson A 《Cellular and molecular life sciences : CMLS》2002,59(3):417-425
Bacillus thuringiensis is distinguished from the very closely related Bacillus cereus and Bacillus anthracis by the presence of several plasmid-encoded δ-endotoxin genes. These δ-endotoxins, synthesized as protoxins, are produced
in large quantities during sporulation and are packaged into intracellular inclusions. Ingestion of the inclusions by insect
larvae leads to protoxin solubilization and conversion to toxins each specific for one of several orders of insects. The toxins
form cation-selective channels in the membrane of cells lining the larval midgut with subsequent lethality. In most cases,
δ-endotoxin synthesis and sporulation are closely coupled. The latter process in B. thuringiensis is probably virtually identical to that in Bacillus subtilis with the additional use of mother cell sporulation forms of RNA polymerase for the synthesis of the δ-endotoxins. There are
other more subtle plasmid-encoded functions or plasmid interactions related to regulating protoxin synthesis. Consideration
of both plasmid and chromosomal genes is thus critical for defining this organism. 相似文献
13.
R. M. H. Ravindranath M. H. Ravindranath M. C. Graves 《Cellular and molecular life sciences : CMLS》1997,53(9):750-758
IgM antibodies directed against neuronal gangliosides GM1 , GM2 , GD1a , GD1b and GT1b occur in normal individuals and their level significantly decreases with age. Patients with lower motor neuron disease (LMND)
produce high levels of these autoantibodies. AntiGM1 IgM is selectively augmented. In these patients, the CD5+ (B1) and CD5− (B2) subsets of B cells are not distinct entities
but range from those without detectable CD5 marker to those with high CD5+ expression. B1 B cells were sorted to homogeneity,
but B2 B cell cannot be isolated to homogeneity because of the presence of B1 cells with low CD5 expression. In short term
cultures both the subsets produced IgM antibodies, but the antibodies reacted better with desialylated GM1 than with GM1 . Cycloheximide (Cx) (0.35 mM) largely blocked IgM synthesis of the B1 B cells but inhibition of the B2 B cells was incomplete,
possibly due to shedding of cytophilic antibodies as well as to the presence of B1 phenotype with loss of CD5 expression.
CD5+ B cells may be involved in the production of antiglycolipid IgM.
Received 9 June 1997; received after revision 21 July 1997; accepted 28 July 1997 相似文献
14.
Small cationic antimicrobial peptides (SCAMPs) as effectors of animal innate immunity provide the first defense against infectious pathogens. This class of molecules exists widely in invertebrate hemolymph and vertebrate skin secretion, but animal venoms are emerging as a new rich resource. Scorpine is a unique scorpion venom defensin peptide that has an extended amino-terminal sequence similar to cecropins. From the African scorpion Opistophthalmus carinatus venom gland, we isolated and identified several cDNAs encoding four new homologs of scorpine (named opiscorpines 1–4). Importantly, we show for the first time the existence of multiple opiscorpine mRNAs with variable 3 untranslated regions (UTRs) in the venom gland, which may be generated by alternative usage of polyadenylation signals. The complete opiscorpine gene structure including its promoter region is determined by genomic DNA amplification. Two large introns were found to be located within the 5 UTR and at the boundary of the mature peptide-coding region. Such a gene structure is distinct, when compared with other scorpion venom peptide genes. However, a comparative promoter analysis revealed that both opiscorpine and scorpion venom neurotoxins share a similar promoter organization. Sequence analysis and structural modeling allow us to group the scorpines and scorpion long-chain K-channel toxins together into one family that shares a similar fold with two distinct domains. The N-terminal cecropin-like domain displaying a clear antimicrobial activity implies that the scorpine family represents a group of real naturally occurring hybrids. Based on the phylogenetic analysis, a possible cooperative interaction between the N and C domains is elucidated, which provides an evolutionary basis for the design of a new class of anti-infectious drugs.Received 5 April 2004; accepted 17 May 2004 相似文献
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16.
Tommy Baumann Lucia Kuhn-Nentwig Carlo R. Largiadèr Wolfgang Nentwig 《Cellular and molecular life sciences : CMLS》2010,67(15):2643-2651
Defensins are a major family of antimicrobial peptides found throughout the phylogenetic tree. From the spider species: Cupiennius salei, Phoneutria reidyi, Polybetes pythagoricus, Tegenaria atrica, and Meta menardi, defensins belonging to the ‘ancestral’ class of invertebrate defensins were cloned and sequenced. The deduced amino acid
sequences contain the characteristic six cysteines of this class of defensins and reveal precursors of 60 or 61 amino acid
residues. The mature peptides consist of 37 amino acid residues, showing up to 70% identities with tick and scorpion defensins.
In C. salei, defensin mRNA was found to be constitutively expressed in hemocytes, ovaries, subesophageal nerve mass, hepatopancreas,
and muscle tissue. This is the first report presenting and comparing antimicrobial peptides belonging to the family of defensins
from spiders. 相似文献
17.
Andrea Venerando Oriano Marin Giorgio Cozza Victor H. Bustos Stefania Sarno Lorenzo Alberto Pinna 《Cellular and molecular life sciences : CMLS》2010,67(7):1105-1118
The ability of three isoforms of protein kinase CK1 (α, γ1, and δ) to phosphorylate the N-terminal region of p53 has been assessed using either recombinant p53 or a synthetic peptide
reproducing its 1–28 sequence. Both substrates are readily phosphoylated by CK1δ and CK1α, but not by the γ isoform. Affinity
of full size p53 for CK1 is 3 orders of magnitude higher than that of its N-terminal peptide (K
m 0.82 μM vs 1.51 mM). The preferred target is S20, whose phosphorylation critically relies on E17, while S6 is unaffected
despite displaying the same consensus (E-x-x-S). Our data support the concept that non-primed phosphorylation of p53 by CK1
is an isoform-specific reaction preferentially affecting S20 by a mechanism which is grounded both on a local consensus and
on a remote docking site mapped to the K221RQK224 loop according to modeling and mutational analysis. 相似文献
18.
Sánchez-Margalet V González-Yanes C Santos-Alvarez J Najib S 《Cellular and molecular life sciences : CMLS》1999,55(1):142-147
Insulin action is initiated by binding to its cognate receptor, which then triggers multiple cellular responses by activating
different signaling pathways. There is evidence that insulin receptor signaling may involve G protein activation in different
target cells. We have studied the activation of G proteins in rat hepatoma (HTC) cells. We found that insulin stimulated binding
of guanosine 5′-O-(3-thiotriphosphate) (GTP-γ-35S) to plasma membrane proteins of HTC cells, in a dose-dependent manner. This effect was completely blocked by pertussis toxin
treatment of the membranes, suggesting the involvement of G proteins of the Gα
i/Gα
o family. The expression of these Gα proteins was checked by Western blotting. Next, we used blocking antibodies to sort out the specific Gα protein activated by insulin stimulation. Anti-Gα
il,2 antibodies completely prevented insulin-stimulated GTP binding, whereas anti-Gα
o,i3 did not modify this effect of insulin on GTP binding. Moreover, we found physical association of the insulin receptor with
Gα
i1,2 by copurification studies. These results further support the involvement of a pertussis toxin-sensitive G protein in insulin
receptor signaling and provides some evidence of specific association and activation of Gα
i1,2 protein by insulin. These findings suggest that Gα
i1,2 proteins might be involved in insulin action.
Received 23 September 1998; received after revision 23 November 1998; accepted 25 November 1998 相似文献
19.
Summary The colonial orb-weaving spider,Eriophora bistriata, coordinates molting cycles through communication. Colonies with differing molting cycles synchronize when combined. Intercycle intervals depend upon food availability. The possible coordination of this synchrony by chemical communication among spiders is discussed. 相似文献
20.
Saha BK Bishayee A Kanjilal NB Chatterjee M 《Cellular and molecular life sciences : CMLS》2001,58(8):1141-1149
The possible promoting effect of streptozotocin (STZ; 65 mg/kg body weight, intraperitoneal)-induced diabetes during 2-acetylaminofluorene
(2-AAF; 0.04% in basal diet)-initiated hepatocarcinogenesis and modulatory effect of 1α,25-dihydroxyvitamin D3 (VD3; 0.3 μg/0.1 ml in propylene glycol, per os) were investigated by monitoring chromosomal aberrations (CAs), DNA strand breaks
and specific DNA adducts in rat liver. VD3 treatment (twice a week) was started 4 weeks before the 2-AAF regimen and continued throughout the study. Aberrant metaphase
chromosomes were counted from the regenerating hepatocytes 15, 30 or 45 weeks after STZ injection, while DNA strand break
and adduct assays were performed 45 days post-STZ treatment. Dietary exposure to 2-AAF elicited a substantial increase in
CAs and elevated the extent of DNA strand breaks and formation of N-(deoxyguanosin-8-yl)-2-aminofluorene. A promoting effect of STZ was evident from CAs coupled with DNA strand break analysis.
VD3 treatment substantially reducted 2-AAF+STZ-induced CAs as well as DNA strand breaks and adducts. Thus, VD3 appears to be effective in suppressing liver-specific early chromosomal as well as DNA damage during the process of rat hepatocarcinogenesis
initiated with 2-AAF and promoted by STZ contributing to its promise as a cancer chemotherapeutic agent.
Received 27 April 2001; accepted 22 May 2001 相似文献