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Venoms constitute complex mixtures of many different molecules arising from evolution in processes driven by continuous prey–predator interactions. One of the most common compounds in these venomous cocktails are pore-forming proteins, a family of toxins whose activity relies on the disruption of the plasmatic membranes by forming pores. The venom of sea anemones, belonging to the oldest lineage of venomous animals, contains a large amount of a characteristic group of pore-forming proteins known as actinoporins. They bind specifically to sphingomyelin-containing membranes and suffer a conformational metamorphosis that drives them to make pores. This event usually leads cells to death by osmotic shock. Sticholysins are the actinoporins produced by Stichodactyla helianthus. Three different isotoxins are known: Sticholysins I, II, and III. They share very similar amino acid sequence and three-dimensional structure but display different behavior in terms of lytic activity and ability to interact with cholesterol, an important lipid component of vertebrate membranes. In addition, sticholysins can act in synergy when exerting their toxin action. The subtle, but important, molecular nuances that explain their different behavior are described and discussed throughout the text. Improving our knowledge about sticholysins behavior is important for eventually developing them into biotechnological tools.
Esperanza Rivera-De-Torre; Juan Palacios-Ortega; J. Peter Slotte; José G. Gavilanes; Álvaro Martínez-Del-Pozo; Sara García-Linares. Functional and Structural Variation Among Sticholysins, Pore-Forming Proteins from the Sea Anemone Stichodactyla helianthus. International Journal of Molecular Sciences 2020, 21, 8915 .
AMA StyleEsperanza Rivera-De-Torre, Juan Palacios-Ortega, J. Peter Slotte, José G. Gavilanes, Álvaro Martínez-Del-Pozo, Sara García-Linares. Functional and Structural Variation Among Sticholysins, Pore-Forming Proteins from the Sea Anemone Stichodactyla helianthus. International Journal of Molecular Sciences. 2020; 21 (23):8915.
Chicago/Turabian StyleEsperanza Rivera-De-Torre; Juan Palacios-Ortega; J. Peter Slotte; José G. Gavilanes; Álvaro Martínez-Del-Pozo; Sara García-Linares. 2020. "Functional and Structural Variation Among Sticholysins, Pore-Forming Proteins from the Sea Anemone Stichodactyla helianthus." International Journal of Molecular Sciences 21, no. 23: 8915.
Actinoporins are a family of pore-forming toxins produced by sea anemones as part of their venomous cocktail. These proteins remain soluble and stably folded in aqueous solution, but when interacting with sphingomyelin-containing lipid membranes, they become integral oligomeric membrane structures that form a pore permeable to cations, which leads to cell death by osmotic shock. Actinoporins appear as multigenic families within the genome of sea anemones: several genes encoding very similar actinoporins are detected within the same species. The Caribbean Sea anemone Stichodactyla helianthus produces three actinoporins (sticholysins I, II and III; StnI, StnII and StnIII) that differ in their toxic potency. For example, StnII is about four-fold more effective than StnI against sheep erythrocytes in causing hemolysis, and both show synergy. However, StnIII, recently discovered in the S. helianthus transcriptome, has not been characterized so far. Here we describe StnIII's spectroscopic and functional properties and show its potential to interact with the other Stns. StnIII seems to maintain the well-preserved fold of all actinoporins, characterized by a high content of β-sheet, but it is significantly less thermostable. Its functional characterization shows that the critical concentration needed to form active pores is higher than for either StnI or StnII, suggesting differences in behavior when oligomerizing on membrane surfaces. Our results show that StnIII is an interesting and unexpected piece in the puzzle of how this Caribbean Sea anemone species modulates its venomous activity.
Esperanza Rivera-De-Torre; Juan Palacios-Ortega; Jessica E. Garb; J. Peter Slotte; José G. Gavilanes; Álvaro Martínez-Del-Pozo. Structural and functional characterization of sticholysin III: A newly discovered actinoporin within the venom of the sea anemone Stichodactyla helianthus. Archives of Biochemistry and Biophysics 2020, 689, 108435 .
AMA StyleEsperanza Rivera-De-Torre, Juan Palacios-Ortega, Jessica E. Garb, J. Peter Slotte, José G. Gavilanes, Álvaro Martínez-Del-Pozo. Structural and functional characterization of sticholysin III: A newly discovered actinoporin within the venom of the sea anemone Stichodactyla helianthus. Archives of Biochemistry and Biophysics. 2020; 689 ():108435.
Chicago/Turabian StyleEsperanza Rivera-De-Torre; Juan Palacios-Ortega; Jessica E. Garb; J. Peter Slotte; José G. Gavilanes; Álvaro Martínez-Del-Pozo. 2020. "Structural and functional characterization of sticholysin III: A newly discovered actinoporin within the venom of the sea anemone Stichodactyla helianthus." Archives of Biochemistry and Biophysics 689, no. : 108435.
Release of aqueous contents from model lipid vesicles has been a standard procedure to evaluate pore formation efficiency by actinoporins, such as sticholysin II (StnII), for the last few decades. However, regardless of the probe of choice, the results reported that StnII action was never able to empty the vesicles completely. This was hard to explain if StnII pores were to be stable and always leaky for the probes used. To address this question, we have used a variety of probes, including rhodamine 6G or Tb3+, to test the permeability of StnII's pores. Our results indicate that calcein was in fact too large to fit through StnII's pores, and that the standard method in the field is actually reporting StnII-induced transient permeation of the membrane rather than the passage of solutes through the stable assembled pores. In order to evaluate the permeability of these structures, we used a dithionite-based assay, which showed that the final pores were in fact open. Thus, our results indicate that the stable actinoporins' pores are open in spite of plateaued classic release curves. Besides the proper pore, the first stages of pore formation would inflict serious damage to living cells as well.
Juan Palacios-Ortega; Esperanza Rivera-De-Torre; José G. Gavilanes; J. Peter Slotte; Álvaro Martínez-Del-Pozo. Evaluation of different approaches used to study membrane permeabilization by actinoporins on model lipid vesicles. Biochimica et Biophysica Acta (BBA) - Biomembranes 2020, 1862, 183311 .
AMA StyleJuan Palacios-Ortega, Esperanza Rivera-De-Torre, José G. Gavilanes, J. Peter Slotte, Álvaro Martínez-Del-Pozo. Evaluation of different approaches used to study membrane permeabilization by actinoporins on model lipid vesicles. Biochimica et Biophysica Acta (BBA) - Biomembranes. 2020; 1862 (9):183311.
Chicago/Turabian StyleJuan Palacios-Ortega; Esperanza Rivera-De-Torre; José G. Gavilanes; J. Peter Slotte; Álvaro Martínez-Del-Pozo. 2020. "Evaluation of different approaches used to study membrane permeabilization by actinoporins on model lipid vesicles." Biochimica et Biophysica Acta (BBA) - Biomembranes 1862, no. 9: 183311.
Animal venoms are complex mixtures of highly specialized toxic molecules. Cnidarians and arachnids produce pore-forming proteins (PFPs) directed against the plasma membrane of their target cells. Among PFPs from cnidarians, actinoporins stand out for their small size and molecular simplicity. While native actinoporins require only sphingomyelin for membrane binding, engineered chimeras containing a recognition antibody-derived domain fused to an actinoporin isoform can nonetheless serve as highly specific immunotoxins. Examples of such constructs targeted against malignant cells have been already reported. However, PFPs from arachnid venoms are less well-studied from a structural and functional point of view. Spiders from the Latrodectus genus are professional insect hunters that, as part of their toxic arsenal, produce large PFPs known as latrotoxins. Interestingly, some latrotoxins have been identified as potent and highly-specific insecticides. Given the proteinaceous nature of these toxins, their promising future use as efficient bioinsecticides is discussed throughout this Perspective. Protein engineering and large-scale recombinant production are critical steps for the use of these PFPs as tools to control agriculturally important insect pests. In summary, both families of PFPs, from Cnidaria and Arachnida, appear to be molecules with promising biotechnological applications.
Esperanza Rivera-De-Torre; Juan Palacios-Ortega; José Gavilanes; Álvaro Martínez-Del-Pozo; Sara García-Linares. Pore-Forming Proteins from Cnidarians and Arachnids as Potential Biotechnological Tools. Toxins 2019, 11, 370 .
AMA StyleEsperanza Rivera-De-Torre, Juan Palacios-Ortega, José Gavilanes, Álvaro Martínez-Del-Pozo, Sara García-Linares. Pore-Forming Proteins from Cnidarians and Arachnids as Potential Biotechnological Tools. Toxins. 2019; 11 (6):370.
Chicago/Turabian StyleEsperanza Rivera-De-Torre; Juan Palacios-Ortega; José Gavilanes; Álvaro Martínez-Del-Pozo; Sara García-Linares. 2019. "Pore-Forming Proteins from Cnidarians and Arachnids as Potential Biotechnological Tools." Toxins 11, no. 6: 370.
Actinoporins are a group of soluble toxic proteins that bind to membranes containing sphingomyelin (SM) and oligomerize to form pores. Sticholysin II (StnII) is a member of the actinoporin family produced by Stichodactyla helianthus. Cholesterol (Chol) is known to enhance the activity of StnII. However, the molecular mechanisms behind this activation have remained obscure, although the activation is not Chol specific but rather sterol specific. To further explore how bilayer lipids affect or are affected by StnII, we have used a multiprobe approach (fluorescent analogs of both Chol and SM) in combination with a series of StnII tryptophan (Trp) mutants to study StnII/bilayer interactions. First, we compared StnII bilayer permeabilization in the presence of Chol or oleoyl-ceramide (OCer). The comparison was done because both Chol and OCer have a 1-hydroxyl, which helps to orient the molecule in the bilayer (although OCer has additional polar functional groups). Both Chol and OCer also have increased affinity for SM, which StnII may recognize. However, our results show that only Chol was able to activate StnII-induced bilayer permeabilization; OCer failed to activate it. To further examine possible Chol/StnII interactions, we measured Förster resonance energy transfer between Trp in StnII and cholestatrienol, a fluorescent analog of Chol. We could show higher Förster resonance energy transfer efficiency between cholestatrienol and Trps in position 100 and 114 of StnII when compared to three other Trp positions further away from the bilayer binding region of StnII. Taken together, our results suggest that StnII was able to attract Chol to its vicinity, maybe by showing affinity for Chol. SM interactions are known to be important for StnII binding to bilayers, and Chol is known to facilitate subsequent permeabilization of the bilayers by StnII. Our results help to better understand the role of these important membrane lipids for the bilayer properties of StnII.
Juan Palacios-Ortega; Sara García-Linares; Esperanza Rivera-De-Torre; José G. Gavilanes; Álvaro Martínez-Del-Pozo; J. Peter Slotte; Esperanza Rivera-De-Torre. Sticholysin, Sphingomyelin, and Cholesterol: A Closer Look at a Tripartite Interaction. Biophysical Journal 2019, 116, 2253 -2265.
AMA StyleJuan Palacios-Ortega, Sara García-Linares, Esperanza Rivera-De-Torre, José G. Gavilanes, Álvaro Martínez-Del-Pozo, J. Peter Slotte, Esperanza Rivera-De-Torre. Sticholysin, Sphingomyelin, and Cholesterol: A Closer Look at a Tripartite Interaction. Biophysical Journal. 2019; 116 (12):2253-2265.
Chicago/Turabian StyleJuan Palacios-Ortega; Sara García-Linares; Esperanza Rivera-De-Torre; José G. Gavilanes; Álvaro Martínez-Del-Pozo; J. Peter Slotte; Esperanza Rivera-De-Torre. 2019. "Sticholysin, Sphingomyelin, and Cholesterol: A Closer Look at a Tripartite Interaction." Biophysical Journal 116, no. 12: 2253-2265.
Juan Palacios Ortega; Sara García-Linares; Esperanza Rivera-De-Torre; Jose G. Gavilanes; Álvaro Martínez-Del-Pozo; J. Peter Slotte. Sticholysins, Sphingomyelin and Cholesterol: A Closer Look into a Tripartite Interaction. Biophysical Journal 2019, 116, 518a .
AMA StyleJuan Palacios Ortega, Sara García-Linares, Esperanza Rivera-De-Torre, Jose G. Gavilanes, Álvaro Martínez-Del-Pozo, J. Peter Slotte. Sticholysins, Sphingomyelin and Cholesterol: A Closer Look into a Tripartite Interaction. Biophysical Journal. 2019; 116 (3):518a.
Chicago/Turabian StyleJuan Palacios Ortega; Sara García-Linares; Esperanza Rivera-De-Torre; Jose G. Gavilanes; Álvaro Martínez-Del-Pozo; J. Peter Slotte. 2019. "Sticholysins, Sphingomyelin and Cholesterol: A Closer Look into a Tripartite Interaction." Biophysical Journal 116, no. 3: 518a.
Transcriptomic profiling of venom producing tissues from different animals is an effective approach for discovering new toxins useful in biotechnological and pharmaceutical applications, as well in evolutionary comparative studies of venomous animals. Stichodactyla helianthus is a Caribbean sea anemone which produces actinoporins as part of its toxic venom. This family of pore forming toxins is multigenic and at least two different isoforms, encoded by separate genes, are produced by S. helianthus. These isoforms, sticholysins I and II, share 93% amino acid identity but differ in their pore forming activity and act synergistically. This observation suggests that other actinoporin isoforms, if present in the venomous mixture, could offer an advantageous strategy to modulate whole venom activity. Using high-throughput sequencing we generated a de novo transcriptome of S. helianthus and determined the relative expression of assembled transcripts using RNA-Seq to better characterize components of this species' venom, focusing on actinoporin diversity. Applying this approach, we have discovered at least one new actinoporin variant from S. helianthus in addition to several other putative venom components.
Esperanza Rivera-De-Torre; Álvaro Martínez-Del-Pozo; Jessica E. Garb. Stichodactyla helianthus' de novo transcriptome assembly: Discovery of a new actinoporin isoform. Toxicon 2018, 150, 105 -114.
AMA StyleEsperanza Rivera-De-Torre, Álvaro Martínez-Del-Pozo, Jessica E. Garb. Stichodactyla helianthus' de novo transcriptome assembly: Discovery of a new actinoporin isoform. Toxicon. 2018; 150 ():105-114.
Chicago/Turabian StyleEsperanza Rivera-De-Torre; Álvaro Martínez-Del-Pozo; Jessica E. Garb. 2018. "Stichodactyla helianthus' de novo transcriptome assembly: Discovery of a new actinoporin isoform." Toxicon 150, no. : 105-114.
Sticholysins I and II (StnI and StnII), α-pore forming toxins from the sea anemone Stichodactyla helianthus, are water-soluble toxic proteins which upon interaction with lipid membranes of specific composition bind to the bilayer, extend and insert their N-terminal α-helix, and become oligomeric integral membrane structures. The result is a pore that leads to cell death by osmotic shock. StnI and StnII show 93% of sequence identity, but also different membrane pore-forming activities. The hydrophobicity profile along the first 18 residues revealed differences which were canceled by substituting StnI amino acids 2 and 9. Accordingly, the StnID9A mutant, and the corresponding StnIE2AD9A variant, showed enhanced hemolytic activity. They also revealed a key role for an exposed salt bridge between Asp9 and Lys68. This interaction is not possible in StnII but appears conserved in the other two well-characterized actinoporins, equinatoxin II and fragaceatoxin C. The StnII mutant A8D showed that this single replacement was enough to transform StnII into a version with impaired pore-forming activity. Overall, the results show the key importance of this salt bridge linking the N-terminal stretch to the β-sandwich core. A conclusion of general application for the understanding of salt bridges role in protein design, folding and stability.
Esperanza Rivera-De-Torre; Juan Palacios-Ortega; Sara García-Linares; José G. Gavilanes; Álvaro Martínez-Del-Pozo. One single salt bridge explains the different cytolytic activities shown by actinoporins sticholysin I and II from the venom of Stichodactyla helianthus. Archives of Biochemistry and Biophysics 2017, 636, 79 -89.
AMA StyleEsperanza Rivera-De-Torre, Juan Palacios-Ortega, Sara García-Linares, José G. Gavilanes, Álvaro Martínez-Del-Pozo. One single salt bridge explains the different cytolytic activities shown by actinoporins sticholysin I and II from the venom of Stichodactyla helianthus. Archives of Biochemistry and Biophysics. 2017; 636 ():79-89.
Chicago/Turabian StyleEsperanza Rivera-De-Torre; Juan Palacios-Ortega; Sara García-Linares; José G. Gavilanes; Álvaro Martínez-Del-Pozo. 2017. "One single salt bridge explains the different cytolytic activities shown by actinoporins sticholysin I and II from the venom of Stichodactyla helianthus." Archives of Biochemistry and Biophysics 636, no. : 79-89.
In this study, we examined the influence of bilayer thickness on the activity of the actinoporin toxins sticholysin I and II (StnI and StnII) at 25 °C. Bilayer thickness was varied using di-monounsaturated phosphatidylcholine (PC) analogs (with 14:1, 16:1, 18:1, 20:1, and 22:1 acyl chains). In addition, N-14:0-sphingomyelin (SM) was always included because StnI and StnII are SM specific. Cholesterol was also incorporated as indicated. In cholesterol-free large unilamellar vesicles (LUV) the PC:SM molar ratio was 4:1, and when cholesterol was included, the complete molar ratio was 4:1:0.5 (PC:SM:cholesterol, respectively). Stn toxins promote bilayer leakage through pores formed by oligomerized toxin monomers. Initial calcein leakage was moderately dependent on bilayer PC acyl chain length (and thus bilayer thickness), with higher rates observed with di-16:1 and di-18:1 PC bilayers. In the presence of cholesterol, the maximum rates of calcein leakage were observed in di-14:1 and di-16:1 PC bilayers. Using isothermal titration calorimetry to study the Stn-LUV interaction, we observed that the bilayer affinity constant (Ka) peaked with LUVs containing di-18:1 PC, and was lower in shorter and longer PC acyl chain bilayers. The presence of cholesterol increased the binding affinity approximately 30-fold at the optimal bilayer thickness (di-18:1-PC). We conclude that bilayer thickness affects both functional and conformational aspects of Stn membrane binding and pore formation. Moreover, the length of the actinoporins' N-terminal α-helix, which penetrates the membrane to form a functional pore, appears to be optimal for the membrane thickness represented by di-18:1 PC.
Juan Palacios-Ortega; Sara García-Linares; Esperanza Rivera-De-Torre; José G. Gavilanes; Álvaro Martínez-Del-Pozo; J. Peter Slotte. Differential Effect of Bilayer Thickness on Sticholysin Activity. Langmuir 2017, 33, 11018 -11027.
AMA StyleJuan Palacios-Ortega, Sara García-Linares, Esperanza Rivera-De-Torre, José G. Gavilanes, Álvaro Martínez-Del-Pozo, J. Peter Slotte. Differential Effect of Bilayer Thickness on Sticholysin Activity. Langmuir. 2017; 33 (41):11018-11027.
Chicago/Turabian StyleJuan Palacios-Ortega; Sara García-Linares; Esperanza Rivera-De-Torre; José G. Gavilanes; Álvaro Martínez-Del-Pozo; J. Peter Slotte. 2017. "Differential Effect of Bilayer Thickness on Sticholysin Activity." Langmuir 33, no. 41: 11018-11027.
Sara García-Linares; Esperanza Rivera-De-Torre; Juan Palacios-Ortega; José G. Gavilanes; Álvaro Martínez-Del-Pozo. The Metamorphic Transformation of a Water-Soluble Monomeric Protein Into an Oligomeric Transmembrane Pore. Advances in Biomembranes and Lipid Self-Assembly 2017, 51 -97.
AMA StyleSara García-Linares, Esperanza Rivera-De-Torre, Juan Palacios-Ortega, José G. Gavilanes, Álvaro Martínez-Del-Pozo. The Metamorphic Transformation of a Water-Soluble Monomeric Protein Into an Oligomeric Transmembrane Pore. Advances in Biomembranes and Lipid Self-Assembly. 2017; ():51-97.
Chicago/Turabian StyleSara García-Linares; Esperanza Rivera-De-Torre; Juan Palacios-Ortega; José G. Gavilanes; Álvaro Martínez-Del-Pozo. 2017. "The Metamorphic Transformation of a Water-Soluble Monomeric Protein Into an Oligomeric Transmembrane Pore." Advances in Biomembranes and Lipid Self-Assembly , no. : 51-97.
Sea anemone actinoporins constitute a protein family of multigene pore-forming toxins (PFT). Equinatoxin II (EqtII), fragaceatoxin C (FraC), and sticholysins I and II (StnI and StnII, respectively), produced by three different sea anemone species, are the only actinoporins whose molecular structures have been studied in depth. These four proteins show high sequence identities and practically coincident three-dimensional structures. However, their pore-forming activity can be quite different depending on the model lipid system employed, a feature that has not been systematically studied before. Therefore, the aim of this work was to evaluate and compare the influence of several distinct membrane conditions on their particular pore-forming behavior. Using a complex model membrane system, such as sheep erythrocytes, StnII showed hemolytic activity much higher than those of the other three actinoporins studied. In lipid model systems, pore-forming ability when assayed against 4:1 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/sphingomyelin (SM) vesicles, with the membrane binding being the rate-limiting step, decreased in the following order: StnI > StnII > EqtII > FraC. When using 1:1:1 DOPC/SM/cholesterol LUVs, the presence of Chol not only enhanced membrane binding affinities by ∼2 orders of magnitude but also revealed how StnII was much faster than the other three actinoporins in producing calcein release. This ability agrees with the proposal that explains this behavior in terms of their high sequence variability along their first 30 N-terminal residues. The influence of interfacial hydrogen bonding in SM- or dihydro-SM-containing bilayers was also shown to be a generalized feature of the four actinoporins studied. It is finally hypothesized that this observed variable ability could be explained as a consequence of their distinct specificities and/or membrane binding affinities. Eventually, this behavior can be modulated by the nature of their natural target membranes or the interaction with not yet characterized isotoxin forms from the same sea anemone species.
Sara García-Linares; Esperanza Rivera-De-Torre; Koldo Morante; Kouhei Tsumoto; Jose M. M. Caaveiro; José G. Gavilanes; J. Peter Slotte; Álvaro Martínez-Del-Pozo. Differential Effect of Membrane Composition on the Pore-Forming Ability of Four Different Sea Anemone Actinoporins. Biochemistry 2016, 55, 6630 -6641.
AMA StyleSara García-Linares, Esperanza Rivera-De-Torre, Koldo Morante, Kouhei Tsumoto, Jose M. M. Caaveiro, José G. Gavilanes, J. Peter Slotte, Álvaro Martínez-Del-Pozo. Differential Effect of Membrane Composition on the Pore-Forming Ability of Four Different Sea Anemone Actinoporins. Biochemistry. 2016; 55 (48):6630-6641.
Chicago/Turabian StyleSara García-Linares; Esperanza Rivera-De-Torre; Koldo Morante; Kouhei Tsumoto; Jose M. M. Caaveiro; José G. Gavilanes; J. Peter Slotte; Álvaro Martínez-Del-Pozo. 2016. "Differential Effect of Membrane Composition on the Pore-Forming Ability of Four Different Sea Anemone Actinoporins." Biochemistry 55, no. 48: 6630-6641.
Actinoporins are pore-forming toxins from sea anemones. Upon interaction with sphingomyelin-containing bilayers, they become integral oligomeric membrane structures that form a pore. Sticholysin II from Stichodactyla helianthus contains five tryptophans located at strategic positions; its role has now been studied using different mutants. Results show that W43 and W115 play a determinant role in maintaining the high thermostability of the protein, while W146 provides specific interactions for protomer–protomer assembly. W110 and W114 sustain the hydrophobic effect, which is one of the major driving forces for membrane binding in the presence of Chol. However, in its absence, additional interactions with sphingomyelin are required. These conclusions were confirmed with two sphingomyelin analogues, one of which had impaired hydrogen bonding properties. The results obtained support actinoporins’ Trp residues playing a major role in membrane recognition and binding, but their residues have an only minor influence on the diffusion and oligomerization steps needed to assemble a functional pore.
Sara García-Linares; Terhi Maula; Esperanza Rivera-De-Torre; José G. Gavilanes; J. Peter Slotte; Álvaro Martínez-Del-Pozo. Role of the Tryptophan Residues in the Specific Interaction of the Sea Anemone Stichodactyla helianthus’s Actinoporin Sticholysin II with Biological Membranes. Biochemistry 2016, 55, 6406 -6420.
AMA StyleSara García-Linares, Terhi Maula, Esperanza Rivera-De-Torre, José G. Gavilanes, J. Peter Slotte, Álvaro Martínez-Del-Pozo. Role of the Tryptophan Residues in the Specific Interaction of the Sea Anemone Stichodactyla helianthus’s Actinoporin Sticholysin II with Biological Membranes. Biochemistry. 2016; 55 (46):6406-6420.
Chicago/Turabian StyleSara García-Linares; Terhi Maula; Esperanza Rivera-De-Torre; José G. Gavilanes; J. Peter Slotte; Álvaro Martínez-Del-Pozo. 2016. "Role of the Tryptophan Residues in the Specific Interaction of the Sea Anemone Stichodactyla helianthus’s Actinoporin Sticholysin II with Biological Membranes." Biochemistry 55, no. 46: 6406-6420.
Among the toxic polypeptides secreted in the venom of sea anemones, actinoporins are pore forming toxins whose toxic activity relies on the formation of oligomeric pores within biological membranes. Intriguingly, actinoporins appear as multigene families which give rise to many protein isoforms in the same individual displaying high sequence identities but large functional differences. However, the evolutionary advantage of producing such similar isotoxins is not fully understood. Here, using sticholysins I and II (StnI and StnII) from the sea anemone Stichodactyla helianthus, it is shown that actinoporin isoforms can potentiate each other′s activity. Through hemolysis and calcein releasing assays, it is revealed that mixtures of StnI and StnII are more lytic than equivalent preparations of the corresponding isolated isoforms. It is then proposed that this synergy is due to the assembly of heteropores since (i) StnI and StnII can be chemically cross-linked at the membrane and (ii) the affinity of sticholysin mixtures for the membrane is increased with respect to any of them acting in isolation, as revealed by isothermal titration calorimetry experiments. These results help to understand the multigene nature of actinoporins and may be extended to other families of toxins that require oligomerization to exert toxicity.
Esperanza Rivera-De-Torre; Sara García Linares; Jorge Alegre-Cebollada; Javier Lacadena; José G. Gavilanes; Álvaro Martínez-Del-Pozo. Synergistic Action of Actinoporin Isoforms from the Same Sea Anemone Species Assembled into Functionally Active Heteropores. Journal of Biological Chemistry 2016, 291, 14109 -14119.
AMA StyleEsperanza Rivera-De-Torre, Sara García Linares, Jorge Alegre-Cebollada, Javier Lacadena, José G. Gavilanes, Álvaro Martínez-Del-Pozo. Synergistic Action of Actinoporin Isoforms from the Same Sea Anemone Species Assembled into Functionally Active Heteropores. Journal of Biological Chemistry. 2016; 291 (27):14109-14119.
Chicago/Turabian StyleEsperanza Rivera-De-Torre; Sara García Linares; Jorge Alegre-Cebollada; Javier Lacadena; José G. Gavilanes; Álvaro Martínez-Del-Pozo. 2016. "Synergistic Action of Actinoporin Isoforms from the Same Sea Anemone Species Assembled into Functionally Active Heteropores." Journal of Biological Chemistry 291, no. 27: 14109-14119.