The Metamorphic Transformation of a Water-Soluble Monomeric Protein Into an Oligomeric Transmembrane Pore

García‐Linares, Sara; Rivera-de-Torre, Esperanza; Palacios-Ortega, Juan; Gavilanes, José G.; Martínez‐del‐Pozo, Álvaro

doi:10.1016/bs.abl.2017.06.004

Cited by 14 publications

(28 citation statements)

References 139 publications

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“…Despite the differences, all of the obtained actinoporins are characterized by a high content of charged and hydrophobic residues at the N-terminal, what is necessary for α-helix formation and penetration into the lipid membrane [ 4 ]. Moreover, the conservativeness of such important for the activity hot spots, as 30SRK32, Lys77, POC-site, and RGD-motive were also found.…”

Section: Resultsmentioning

confidence: 99%

“…H. crispa actinoporins were found to differ from one another by single substitutions that were localized both in the N-terminal region (1–27 aa) and at the β-core (28–177 aa) ( Figure 2 ). A lot of actinoporin studies are devoted to the investigation of the amphiphilic N-terminal region hydrophobicity [ 4 , 20 , 75 ]. Here, we focus on the dissection of the molecular surface electrostatic potential and on the revealing of a role of certain charged residues in the pore-formation.…”

Section: Resultsmentioning

confidence: 99%

“…Actinoporins are biologically active polypeptides (17–20 kDa) that are found in sea anemones [ 1 , 2 , 3 , 4 , 5 ]. Their structure includes compact β-fold, without disulfide bonds, formed by 12 β-sheets and two α-helices, one of which, functional and more extended, is located at the N-terminus, and the second one, short, is at the C-terminus [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…[ 11 , 29 , 35 , 36 , 37 , 39 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ]. In general, the process of pore formation by actinoporins involves its binding to a sphingomyelin of cytoplasmic membranes through the aromatic POC site, transition of a N-terminal α-helical region (1–25 aa) to the lipid-water interface, oligomerization of 3–4, 8, or 9 monomers within the membrane interface, and the insertion of the N-terminal region into membrane hydrophobic core resulted in the creation of the functionally active protein-lipid pore [ 4 ]. Actinoporin conformational transformation from the soluble state to the membrane-binding one is a fundamental α-PFT property that is directed at the disruption of biological targets [ 41 , 54 ].…”

Section: Introductionmentioning

confidence: 99%

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Multigene Family of Pore-Forming Toxins from Sea Anemone Heteractis crispa

et al. 2018

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Sea anemones produce pore-forming toxins, actinoporins, which are interesting as tools for cytoplasmic membranes study, as well as being potential therapeutic agents for cancer therapy. This investigation is devoted to structural and functional study of the Heteractis crispa actinoporins diversity. Here, we described a multigene family consisting of 47 representatives expressed in the sea anemone tentacles as prepropeptide-coding transcripts. The phylogenetic analysis revealed that actinoporin clustering is consistent with the division of sea anemones into superfamilies and families. The transcriptomes of both H. crispa and Heteractis magnifica appear to contain a large repertoire of similar genes representing a rapid expansion of the actinoporin family due to gene duplication and sequence divergence. The presence of the most abundant specific group of actinoporins in H. crispa is the major difference between these species. The functional analysis of six recombinant actinoporins revealed that H. crispa actinoporin grouping was consistent with the different hemolytic activity of their representatives. According to molecular modeling data, we assume that the direction of the N-terminal dipole moment tightly reflects the actinoporins’ ability to possess hemolytic activity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Multigene Family of Pore-Forming Toxins from Sea Anemone Heteractis crispa

et al. 2018

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“…PFPs remain stably folded and soluble in water but, upon interaction with the membrane of their target cells—and after recognition of a receptor that can be a sugar, a protein, or even a specific lipid—they polymerize into an oligomeric transmembrane protein that makes a pore. We, and other authors, even speak of a molecular metamorphosis transforming these toxins from water-soluble to transmembrane proteins, escaping the aforementioned classification [8,9,10]. Attachment to the membrane increases the local concentration of the toxin, reducing protein diffusion to a bidimensional system, and thus facilitating the oligomerization that leads to pore formation.…”

Section: Pore-forming Proteins (Pfps)mentioning

confidence: 99%

Pore-Forming Proteins from Cnidarians and Arachnids as Potential Biotechnological Tools

Rivera-de-Torre

Palacios-Ortega

Gavilanes

et al. 2019

Toxins

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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.

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Sticholysin I–II oligomerization in the absence of membranes

et al. 2022

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Sticholysins are pore-forming toxins produced by the sea anemone Stichodactyla helianthus. When they encounter a sphingomyelin-containing membrane, these proteins bind to it and oligomerize, a process that ends in pore formation. Mounting evidence indicates that StnII can favour the activity of StnI. Previous results have shown that these two isotoxins can oligomerize together. Furthermore, StnII appeared to potentiate the activity of StnI through the membrane-binding step of the process. Hence, isotoxin interaction should occur prior to membrane encounter. Here, we have used analytical ultracentrifugation to investigate the oligomerization of Stns in solution, both separately and together. Our results indicate that while StnI seems to be more prone to oligomerize in water solution than StnII, a small percentage of StnII in StnI-StnII mixtures promotes oligomerization.

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The Metamorphic Transformation of a Water-Soluble Monomeric Protein Into an Oligomeric Transmembrane Pore

Cited by 14 publications

References 139 publications

Multigene Family of Pore-Forming Toxins from Sea Anemone Heteractis crispa

Multigene Family of Pore-Forming Toxins from Sea Anemone Heteractis crispa

Pore-Forming Proteins from Cnidarians and Arachnids as Potential Biotechnological Tools

Sticholysin I–II oligomerization in the absence of membranes

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