Production of the spore-delta-endotoxin complex by variants of bacillus thuringiensis in two fermentation media.
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Bacillus↗
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Dynamics underlying rhythmic and non-rhythmic variants of abnormal, waking delta activity.
OBJECT: We applied a new test, nonlinear cross prediction (NLCP), to investigate whether or polymorphic delta activity (PDA) and frontal intermittent rhythmic delta activity (FIRDA) reflect linear or nonlinear brain dynamics. Furthermore realistic models were constructed to explain the dynamical properties of PDA and FIRDA. METHODS: Forty-nine EEG time series with FIRDA and 40 time series with PDA were studied with the NLCP algorithm. This characterizes a time series in terms of its predictability, amplitude asymmetry, and time asymmetry, with the latter two measures reflecting nonlinearity. Parameters of an EEG model proposed by Lopes da Silva were adjusted to obtain time series resembling PDA and FIRDA. RESULTS: FIRDA was more predictable than PDA. Most PDA segments could not be distinguished from linearly filtered noise. In contrast, FIRDA activity showed strong evidence of nonlinear dynamics. These dynamical properties of PDA and FIRDA could be reproduced by the Lopes da Silva model. PDA and FIRDA reflect a point attractor and a limit cycle attractor, respectively, perturbed by dynamical noise. CONCLUSION: Experimental analysis and modeling of the data suggest that PDA and FIRDA reflect fundamentally different types of brain dynamics. While PDA is filtered noise, reflecting low-level, random input to cortical networks, FIRDA may reflect limit-cycle oscillations due to increased excitation.
Adult↗
The deltaccr5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe.
The chemokine receptor CCR5 is encoded by the CMKBR5 gene located on the p21.3 region of human chromosome 3, and constitutes the major co-receptor for the macrophage-tropic strains of HIV-1. A mutant allele of the CCR5 gene, Delta ccr5 , was shown to provide to homozygotes with a strong resistance against infection by HIV. The frequency of the Delta ccr5 allele was investigated in 18 European populations. A North to South gradient was found, with the highest allele frequencies in Finnish and Mordvinian populations (16%), and the lowest in Sardinia (4%). Highly polymorphic microsatellites (IRI3.1, D3S4579 and IRI3.2, D3S4580 ) located respectively 11 kb upstream and 68 kb downstream of the CCR5 gene deletion were used to determine the haplotype of the chromosomes carrying the Delta ccr5 variant. A strong linkage disequilibrium was found between Delta ccr5 and specific alleles of the IRI3.1 and IRI3.2 microsatellites: >95% of the Delta ccr5 chromosomes carried the IRI3.1-0 allele, while 88% carried the IRI3.2-0 allele. These alleles were found respectively in only 2 or 1.5% of the chromosomes carrying a wild-type CCR5 gene. From these data, it was inferred that most, if not all Delta ccr5 alleles originate from a single mutation event, and that this mutation event probably took place a few thousand years ago in Northeastern Europe. The high frequency of the Delta ccr5 allele in Caucasian populations cannot be explained easily by random genetic drift, suggesting that a selection advantage is or has been associated with homo- or heterozygous carriers of the Delta ccr5 allele.
Acquired Immunodeficiency Syndrome↗
Effect of recombinant human fibroblast interferon and mezerein on growth, differentiation, immune interferon binding and tumor associated antigen expression in human melanoma cells.
The combination of recombinant human fibroblast interferon (INF-delta) and the antileukemic compound mezerein (MEZ) results in a synergistic suppression in the growth of human melanoma cells and a concomitant increase in melanin synthesis. In the present study we have further analyzed this synergistic interaction and have also evaluated the effect of IFN-delta and MEZ, alone and in combination, on recombinant human gamma interferon (IFN-gamma) binding and Class I HLA and melanoma associated antigen (MAA) expression in the HO-1 human melanoma cell line. Single cell clones isolated from the HO-1 cell line varied in their sensitivity to the antiproliferative effects of IFN-delta and MEZ. With all twelve clones, however, the combination of IFN-delta plus MEZ was more growth inhibitory than either agent used alone, even in HO-1 subclones displaying relative resistance to IFN-delta. By continuous growth in gradually increasing concentrations of IFN-delta, a variant population of HO-1 cells, HO-1 delta R-D, was generated which was more resistant to the antigrowth effects of IFN-delta than the original HO-1 parental cell line. In the IFN delta R-D cell line the combination of IFN-delta plus MEZ synergistically suppressed growth. Exposure of HO-1 cells to 2500 units/ml IFN-delta or 50 ng/ml MEZ for 96 hr resulted in no change or an increase in the binding of labelled IFN-gamma to surface receptors, whereas the combination of IFN-delta plus MEZ increased IFN-gamma binding 2-to-4-fold in HO-1 cells. This increase was the result of an increase in the number of receptors on treated cells coupled with a protection against a decrease in receptors observed for confluent untreated cells. Changes in IFN-gamma binding resulting from treatment with IFN-delta plus MEZ were not associated with alterations in the binding affinity of INF-gamma to its receptor. Changes were also observed in the expression of HLA Class I antigens and MAAs following treatment of HO-1 cells with IFN-delta, MEZ or IFN-delta plus MEZ. IFN-delta and MEZ increased the expression of HLA Class I antigens a 96 kd MAA defined by MoAb CL203, a 100 kd MAA defined by MoAb 376.96 and a 115 kd MAA defined by MoAb 345.134 but decreased the expression of a high molecular weight-melanoma associated antigen (HMW-MAA) defined by MoAb 325.28S.(ABSTRACT TRUNCATED AT 400 WORDS)
Antigens, Neoplasm↗
Native tertiary structure in an A-state.
The A-state is an equilibrium species that is thought to represent the molten globule, an on-pathway protein folding intermediate with native secondary structure and non-native, fluctuating tertiary structure. We used yeast iso-1-ferricytochrome c to test for an evolutionary-invariant tertiary interaction in its A-state. Thermal denaturation monitored by circular dichroism (CD)spectropolarimetry was used to determine A-state and native-state stabilities, delta GA reversible D and delta GN reversible D. We examined the wild-type protein, seven variants with substitutions at the interface between the N and C-terminal helices, and four control variants. The controls have the same amino acid changes as the interface variants, but the changes are close to, not at, the interface. We also examined the pH and sulfate concentration dependencies and found that while these factors affect the far-UV CD spectra of the least stable variants, they do not alter the difference in stability between the wild-type protein and the variants. A delta GA reversible D versus-delta GN reversible D plot for the interface variants has a slope near unity and the control variants have near-wild-type stability. These results show that the helix-helix interaction stabilizes the A-state and the native state to the same degree, confirming our preliminary report. We determined that the heat capacity change for A-state denaturation is approximately 60% of the value for native-state denaturation, indicating that the A-state interior is native-like. We discuss our results in relation to ferricytochrome c folding kinetics.
Cytochrome c Group↗
Screening for naturally occurring apolipoprotein A-I variants: apo A-I(delta K107) is associated with low HDL-cholesterol levels in men but not in women.
Isoelectric focussing (IEF) in carrier ampholyte-generated pH gradients and hybrid isoelectric focussing (HIEF) in immobilized pH gradients under nondenaturing conditions were used in parallel to screen 5,500 plasma samples for naturally occurring variants of apolipoprotein A-I (apo A-I). The following defects were identified in four unrelated subjects heterozygous for apo A-I variants: apo A-I(delta K107)(2 x), apo A-I(K107M)(1 x), and apo A-I(E41R)(1 x). The later variant is a novel finding. Family studies did not reveal any association of apo A-I(K107M) and apo A-I(E41R) with dyslipidemia, but identified several heterozygotes for apo A-I(delta K107) who had low levels of high density lipoprotein (HDL)-cholesterol. Therefore, and since the apo A-I(delta K107) is the most frequent apo A-I variant in Germany (1: 5,000) we evaluated our data and that reported from 11 families with 32 heterozygous carriers and 30 unaffected controls. This analysis revealed that apo A-I(delta K107) is associated with lower HDL-cholesterol (-30%) and higher triglycerides (+48%) in men but not in women as compared with unaffected family members as well as with controls from the Prospective Cardiovascular Münster (PROCAM) study. Moreover, 11 of 15 male apo A-I(delta K107) heterozygotes but only 2 of 17 female apo A-I(delta K107) heterozygotes had HDL-cholesterol levels below the 20th percentile of sex-matched controls from the PROCAM study. We conclude that heterozygosity for apo A-I(delta K107) decreases HDL-cholesterol and increases triglycerides in men but not in women.
Apolipoprotein A-I↗
Pit-1/growth hormone factor 1 splice variant expression in the rhesus monkey pituitary gland and the rhesus and human placenta.
We have examined the expression of Pit-1 messenger RNA (mRNA) splice variants in the nonhuman primate pituitary and in rhesus and human placenta. Full-length complementary DNAs (cDNAs) representing Pit-1 and the Pit-1 beta splice variants were cloned from a rhesus monkey pituitary cDNA library and were readily detectable by RT-PCR with rhesus pituitary gland RNA. The Pit-1T variant previously reported in mouse pituitary tumor cell lines was not detectable in normal rhesus pituitary tissue, although two novel splice variants were detected. A cDNA approximating the rat Pit-1 delta 4 variant was cloned but coded for a truncated and presumably nonfunctional protein. Only by using a nested RT-PCR approach were Pit-1 and Pit-1 beta variants consistently detectable in both human and rhesus placental tissue. The Pit-1 beta variant mRNA was not detectable in JEG-3 choriocarcinoma cells unless the cells were stimulated with 8-Br-cAMP. Immunoblot studies with nuclear extracts from primary rhesus syncytiotrophoblast cultures or JEG-3 choriocarcinoma cells indicated that although mRNA levels were very low, Pit-1 protein was detectable in differentiated cytotrophoblasts, and levels increased after treatment with 8-Br-cAMP. Two major species of Pit-1 protein were detected that corresponded to the two major bands in rat pituitary GH3 cell nuclear extracts. Low levels of slightly larger bands also were seen, which may represent Pit-1 beta protein or phosphorylated species. We conclude that Pit-1 splice variants expressed in the primate pituitary gland differ from those in the rodent gland and that the Pit-1 and Pit-1 beta mRNAs expressed in the placenta give rise to a pattern of protein expression similar to that seen in pituitary cells, which is inducible by treatment with 8-Br-cAMP.
Amino Acid Sequence↗
The high frequency of the Hb B2 variant in the Herero population: a founder effect?
The beta-globin gene cluster haplotype associated with the delta-globin variant Hb B2 was determined in Herero individuals from six different families, in order to establish whether founder effect was responsible for the high frequency of this variant in the population. The electrophoretic detection of Hb B2 was confirmed at the molecular level by polymerase chain reaction, followed by Cfo I digestion. The haplotype associated with the Hb B2 chromosome was determined in two families, and was shown to be the same. In the remaining four families the haplotypes could not be established conclusively, but were consistent with the haplotype observed in the other two families. The high gene frequency of Hb B2 is thus likely to have resulted form founder effect.
Black People↗
Use of the delta-P1 approximation for recovery of optical absorption, scattering, and asymmetry coefficients in turbid media.
We introduce a robust method to recover optical absorption, reduced scattering, and single-scattering asymmetry coefficients (microa, micro's, g1) of infinite turbid media over a range of (micro's/microa) spanning 3 orders of magnitude. This is accomplished through the spatially resolved measurement of irradiance at source-detector separations spanning 0.25-8 transport mean free paths (l*). These measurements are rapidly processed by a multistaged nonlinear optimization algorithm in which the measured irradiances are compared with predictions given by the delta-P1 variant of the diffusion approximation to the Boltzmann transport equation. The ability of the delta-P1 model to accurately describe radiative transport within media of arbitrary albedo and on spatial scales comparable to l* is the key element enabling the separation of g1 from micro's.
Algorithms↗
Role of CD3 delta in surface expression of the TCR/CD3 complex and in activation for killing analyzed with a CD3 delta-negative cytotoxic T lymphocyte variant.
The TCR is composed of two chains (alpha/beta) containing variable regions associated at the cell surface with invariant chains (CD3 gamma-, delta-, epsilon-, and zeta/eta chains). The latter control assembly and surface expression of the TCR/CD3 complex, as well as its cytoplasmic association with signal transduction relays. In differentiated CTL, stimulation through the TCR leads to the transcriptional activation of genes coding secreted cytokines such as gamma-IFN as well as transcription-independent activation of the lytic machinery. It is not known which of the CD3 components is necessary to transduce the required signals. CD3 gamma- and delta-chains have high sequence homology, in particular in their cytoplasmic domain, and it has been proposed that alpha beta gamma epsilon zeta and alpha beta delta, epsilon zeta may be expressed and function in signal transduction independently. Here, we characterize a CTL clone that has selectively lost expression of the CD3 delta mRNA. This results in expression of partial CD3 complexes devoid of TCR alpha beta chains at the surface of the clone, which are not functional for activation of cytolysis or for gamma-IFN production. Transfection of the clone with either the native or a cytoplasmic exon-deleted CD3 delta gene restores full TCR/CD3 surface expression as well as Ag- or CD3-mediated activation for killing and for gamma-IFN production, indicating that the CD3 delta chain is essential for surface expression of the TCR alpha beta, but that the CD3 delta cytoplasmic portion is not required either for complex assembly or for signal transduction involved in the functions studied.
Amino Acid Sequence↗
Identification and cDNA sequence of delta-preprotachykinin, a fourth splicing variant of the rat substance P precursor.
The neuropeptides substance P and neurokinin A are synthesised from a family of precursor polypeptides encoded by the preprotachykinin A (PPT) gene. In addition to a mRNA (beta-PPT) containing all 7 exons of the gene, alternatively spliced mRNAs lacking either exon 4 (gamma-PPT) or exon 6 (alpha-PPT) have been identified. We have determined the sequences of cDNA clones encoding four variants of PPT mRNA from rat dorsal root ganglion (DRG), including a novel mRNA species (delta-PPT) in which both exons 4 and 6 are absent. The sequence of delta-PPT predicts the existence of a novel tachykinin precursor polypeptide.
Amino Acid Sequence↗
Structural basis for difference in heat capacity increments for Ca(2+) binding to two alpha-lactalbumins.
Thermodynamic parameters for the unfolding of as well as for the binding of Ca(2+) to goat alpha-lactalbumin (GLA) and bovine alpha-lactalbumin (BLA) are deduced from isothermal titration calorimetry in a buffer containing 10 mM Tris-HCl, pH 7.5 near 25 degrees C. Among the different parameters available, the heat capacity increments (Delta C(p)) offer the most direct information for the associated conformational changes of the protein variants. The Delta C(p) values for the transition from the native to the molten globule state are rather similar for both proteins, indicating that the extent of the corresponding conformational change is nearly identical. However, the respective Delta C(p) values for the binding of Ca(2+) are clearly different. The data suggest that a distinct protein region is more sensitive to a Ca(2+)-dependent conformational change in BLA than is the case in GLA. By analysis of the tertiary structure we observed an extensive accumulation of negatively charged amino acids near the Ca(2+)-binding site of BLA. In GLA, the cluster of negative charges is reduced by the substitution of Glu-11 by Lys. The observed difference in Delta C(p) values for the binding of Ca(2+) is presumably in part related to this difference in charge distribution.
Amino Acid Sequence↗
Linkage relationships between beta- and delta-structural loci and African forms of beta thalassaemia.
Five families are described in which there have been matings between individuals doubly heterozygous for beta thalassaemia and the delta-chain variant haemoglobin A2' to normal persons. In all there were 24 informative offspring. There were no crossovers between the beta-thalassaemia and delta-chain loci; in three of the families the genes were linked in cis and in two families the genes were found in trans. Together with previously reported families there have now been 58 opportunities for crossing over between the beta-thalassaemia and delta-chain loci and there have been two possible and one highly probable crossovers. Of the total of 9 families reported to date 4 have had the genes for beta thalassaemia and Hb A2' in cis and 5 in trans. These findings are contrasted with the findings in families where a beta-chain structural variant and Hb A2' have been observed together and these genes have always been found in trans and never in cis. The reasons for linkage disequilibrium of this type are discussed. It is concluded tentatively that the distance between the delta-structural and beta-thalassaemia loci is greater than that between the delta-structural and beta-structural loci. To date this conclusion can only be applied to the beta+ -thalassaemia and beta-thalassaemia genes as found in the African population, since this is the only population with a high incidence of delta-chain mutants which allow linkage analysis of this type to be carried out.
Africa↗
Studies of the processing of the protease which initiates degradation of small, acid-soluble proteins during germination of spores of Bacillus species.
Three mutant forms of the protease (GPR) that initiates degradation of small, acid-soluble spore proteins (SASP) during germination of spores of Bacillus species have been generated. In one variant (GPR delta), the putative pro sequence removed in conversion of the GPR zymogen (termed P46) to the active enzyme (termed P41) was deleted. GPR delta was expressed in both Escherichia coli and Bacillus subtilis as a polypeptide of 41 kDa (P41) which was active both in vivo and in vitro. The other two variants had changes in the sequence around the site where the pro sequence is removed, making this sequence even more like that recognized and cleaved by GPR in its SASP substrates. One of these variants (GPRS) was synthesized as P46S in both B. subtilis and E. coli, but P46S was processed to P41S earlier in B. subtilis sporulation than was wild-type P46. The second variant (GPREI) was made as P46EI but underwent extremely rapid processing to P41EI in both E. coli and B. subtilis. Expression of elevated (> 100-fold) levels of GPR delta or GPREI blocked sporulation at the time of synthesis of glucose dehydrogenase. Expression of elevated levels of GPRS or low levels (< 20% of the wild-type level) of GPR delta or GPREI did not retard sporulation, but the SASP level in the resultant spores was greatly reduced. Prolonged incubation of P41 delta, P41EI, or wild-type P41, either in vivo or with purified proteins in vitro, resulted in a second self-cleavage event generating a 39-kDa polypeptide termed P39. The sequence in the P(41)-->P(39) cleavage site was also quite similar to that recognized and cleaved by GPR in SASP. Together, these results strongly support a model in which activation of GPR during sporulation by conversion of P(46) to P(41) is a self-processing event triggered by a change in the spore core environment (i.e., dehydration) which precludes attack of the active P(41) on its SASP substrates. However, in the first minutes of spore germination, rapid spore core hydration allows rapid attack of active GPR on SASP.
Amino Acid Sequence↗
Mutants from V79 fibroblasts exhibiting hypersensitivity to aphidicolin and 3'-azido-3'-deoxythymidine.
One variant, aphhs-3 was previously isolated based on a hypersensitivity to nontoxic concentrations of aphidicolin, a specific inhibitor of DNA polymerases-alpha and delta. This variant was found to be more sensitive to temperatures above 35 degrees C and to 10 microM of 3'-azido-3'-deoxythymidine (zidovudine, azidothymidine, or AZT) than the parental 743x cells. DNA polymerase activities in the cell extract or in the partially purified fraction by DEAE-cellulose (DE52) anion exchange column from aphhs-3 were active at 40 degrees C. No significant differences in deoxynucleoside triphosphate pools were observed at 34 degrees C for both the parental 743x and aphhs-3 cells. Revertants were isolated at 39 degrees C: six revertants (aphhs-3-tr1 through aphhs-3-tr6) were obtained without aphidicolin; one revertant aphhs-3-tar (the tar clone) was selected in aphidicolin (0.12 microM). The hypersensitivity to aphidicolin (Aphhs) and AZT (AZThs) was cosegregated in the revertant aphhs-3-tr5 (the tr5 clone), while the tar clone was not AZThs. There was a similar increase in the specific activity of 3H-labeled DNA in all cell lines after additions of [3H]AZT or [3H]thymidine. Additions of purine or pyrimidine arabinosides (araT, araC, and araA) to all cell lines resulted in a similar cytotoxicity, suggesting the anabolism of dTTP was not defective in the tr5 clone. The spontaneous mutation rate at the hypoxanthine-guanine phosphoryltransferase locus using replating techniques and 6-thioguanine resistance selection was less than or equal to 5 x 10(-7), 2.2 x 10(-6), or 1.3 x 10(-6) per generation for the tr5, 743x, or tar cell lines, respectively. Most importantly, DNA polymerase activities in the cell extract of the revertant tr5 clone were inhibited by 0.5 microM AZTTP. In contrast, no inhibition was observed in those of the parental 743x and revertant tar cells. The cosegregation of both Aphhs and AZThs in the tr5 revertant suggests that these two phenotypes may be a result of the same mutational event.
Animals↗
Autoinhibitory regulation of p73 by Delta Np73 to modulate cell survival and death through a p73-specific target element within the Delta Np73 promoter.
p73 is a p53-related tumor suppressor but is also induced by oncogene products such as E2F-1, raising a question as to whether p73 is a tumor suppressor gene or oncogene. Unlike p53, p73 has several variants, including Delta Np73, which lacks the NH(2)-terminal transactivation domain. Although, in developing neurons, Delta Np73 is expressed abundantly and seems to inhibit the proapoptotic function of p53, the role of p73 and Delta Np73 and their regulatory mechanism in cell growth and differentiation are poorly understood. Here we report that p73, but not p53, directly activates the transcription of endogenous Delta Np73 by binding to the p73-specific target element located at positions -76 to -57 within the Delta Np73 promoter region. The activation of Delta Np73 promoter by p63 was marginal. Delta Np73 was associated with p73 alpha, p73 beta, and p53, as demonstrated by immunoprecipitation assays, and inhibited their transactivation activities when we used reporters of Mdm2, Bax, or Delta Np73 itself in SAOS-2 cells. Furthermore, induction or overexpression of Delta Np73 promoted cell survival by competing with p53 and p73 itself. Thus, our results suggest that the negative feedback regulation of p73 by its target Delta Np73 is a novel autoregulatory system for modulating cell survival and death.
Animals↗
Inhibition of tryptase TL2 from human T4+ lymphocytes and inhibition of HIV-1 replication in H9 cells by recombinant aprotinin and bikunin homologues.
The serine esterase TL2 from human T4+ lymphocytes is a binding component to HIV-1 glycoprotein gp120 and seems to play a role in the HIV-1 infection mechanism. Recombinant variants of the Kunitz-type serine proteinase inhibitor aprotinin were investigated for their ability to inhibit tryptase TL2 and the binding of gp120 to this enzyme. Furthermore, the viral replication of HIV-1 was investigated H9 cell cultures under the influence of recombinant aprotinin and bikunin variants. In contrast to native aprotinin, the recombinant variant [Arg15, Phe17, Glu52] aprotinin with a reactive-site sequence homologous to the V3 loop of HIV-1 gp120 showed a specific inhibition of tryptase TL2 (> 80%). However, the [Leu15, Phe17, Glu52] aprotinin variant with hydrophobic subsites was the most potent inhibitor of the binding of gp120 to tryptase TL2 (68%). Our results show that the enzyme activity of purified tryptase TL2 is inhibited not only by variants with basic amino acids, but also those with hydrophobic residues in the reactive-site region. Therefore, tryptase TL2 is not a typical trypsin-like or chymotrypsin-like protease. Investigations on inhibition of HIV-1 replication in H9 cell cultures showed that tryptase TL2 is involved in the mechanism of virus internalization into human lymphocytes. The [Leu15, Phe17, Glu52] aprotinin showed a significant retardation of syncytium formation over a period of 5 days in a 1 micro M concentration. Similar investigations were performed with recombinant variants of bikunin, the light chain of human inter-alpha-trypsin inhibitor. Only the single-headed variant [Arg94] delta 2 bikunin inhibited slightly the syncytium formation over a period of 2 days in a 2.2 micro M concentration. Wild-type bikunin and all full-length variants showed no effect, possibly due to steric hindrance by the second domain of the double-headed inhibitor.
Amino Acid Sequence↗
A spider toxin that induces a typical effect of scorpion alpha-toxins but competes with beta-toxins on binding to insect sodium channels.
Delta-palutoxins from the spider Paracoelotes luctuosus (Araneae: Amaurobiidae) are 36-37 residue long peptides that show preference for insect sodium channels (NaChs) and modulate their function. Although they slow NaCh inactivation in a fashion similar to that of receptor site 3 modifiers, such as scorpion alpha-toxins, they actually bind with high affinity to the topologically distinct receptor site 4 of scorpion beta-toxins. To resolve this riddle, we scanned by Ala mutagenesis the surface of delta-PaluIT2, a delta-palutoxin variant with the highest affinity for insect NaChs, and compared it to the bioactive surface of a scorpion beta-toxin. We found three regions on the surface of delta-PaluIT2 important for activity: the first consists of Tyr-22 and Tyr-30 (aromatic), Ser-24 and Met-28 (polar), and Arg-8, Arg-26, Arg-32, and Arg-34 (basic) residues; the second is made of Trp-12; and the third is made of Asp-19, whose substitution by Ala uncoupled the binding from toxicity to lepidopteran larvae. Although spider delta-palutoxins and scorpion beta-toxins have developed from different ancestors, they show some commonality in their bioactive surfaces, which may explain their ability to compete for an identical receptor (site 4) on voltage-gated NaChs. Yet, their different mode of channel modulation provides a novel perspective about the structural relatedness of receptor sites 3 and 4, which until now have been considered topologically distinct.
Alanine↗