6k2g

From Proteopedia

Structure of FraE in the monomer state

Structural highlights

6k2g is a 2 chain structure with sequence from Actinia fragacea. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.22Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ACTPC_ACTFR Pore-forming protein that forms cations-selective hydrophilic pores of around 1 nm and causes cardiac stimulation and hemolysis. Pore formation is a multi-step process that involves specific recognition of membrane sphingomyelin (but neither cholesterol nor phosphatidylcholine) using aromatic rich region and adjacent phosphocholine (POC) binding site, firm binding to the membrane (mainly driven by hydrophobic interactions) accompanied by the transfer of the N-terminal region to the lipid-water interface and finally pore formation after oligomerization of several monomers.^[1]

Publication Abstract from PubMed

Random mutations and selective pressure drive protein adaptation to the changing demands of the environment. As a consequence, nature favors the evolution of protein diversity. A group of proteins subject to exceptional environmental stress and known for their widespread diversity are the pore-forming hemolytic proteins from sea anemones, known as actinoporins. In this study, we identified and isolated new isoforms of actinoporins from the sea anemone Actinia fragacea (fragaceatoxins). We characterized their hemolytic activity, examined their stability and structure, and performed a comparative analysis of their primary sequence. Sequence alignment reveals that most of the variability among actinoporins is associated with non-functional residues. The differences in the thermal behavior among fragaceatoxins suggest that these variability sites contribute to changes in protein stability. In addition, the protein-protein interaction region showed a very high degree of identity (92%) within fragaceatoxins, but only 25% among all actinoporins examined, suggesting some degree of specificity at the species level. Our findings support the mechanism of evolutionary adaptation in actinoporins and reflect common pathways conducive to protein variability.

The Isolation of New Pore-Forming Toxins from the Sea Anemone Actinia fragacea Provides Insights into the Mechanisms of Actinoporin Evolution.,Morante K, Bellomio A, Viguera AR, Gonzalez-Manas JM, Tsumoto K, Caaveiro JMM Toxins (Basel). 2019 Jul 10;11(7). pii: toxins11070401. doi:, 10.3390/toxins11070401. PMID:31295915^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bellomio A, Morante K, Barlic A, Gutierrez-Aguirre I, Viguera AR, Gonzalez-Manas JM. Purification, cloning and characterization of fragaceatoxin C, a novel actinoporin from the sea anemone Actinia fragacea. Toxicon. 2009 Nov;54(6):869-80. doi: 10.1016/j.toxicon.2009.06.022. Epub 2009 Jun, 27. PMID:19563820 doi:10.1016/j.toxicon.2009.06.022
↑ Morante K, Bellomio A, Viguera AR, Gonzalez-Manas JM, Tsumoto K, Caaveiro JMM. The Isolation of New Pore-Forming Toxins from the Sea Anemone Actinia fragacea Provides Insights into the Mechanisms of Actinoporin Evolution. Toxins (Basel). 2019 Jul 10;11(7). pii: toxins11070401. doi:, 10.3390/toxins11070401. PMID:31295915 doi:http://dx.doi.org/10.3390/toxins11070401