| Structural highlights
Function
[TXL_EISFE] Pore-forming toxin that specifically binds sphingomyelin in the plasma membrane of various cells. Has hemolytic activity. Is also cytotoxic to spermatozoa of some species of invertebrates and many species of vertebrates and to amphibian larvae, guinea pig polymorphonuclear leukocytes, chicken fibroblasts, normal spleen cells and various tumor cells. Is lethal for various species of reptiles, amphibian, birds and mammals. Induces smooth muscle contraction. It binds sphingomyelin and induces hemolysis in the same manner as lysenin-related protein 2, and is 10 times more effective than lysenin-related protein 1.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
Lysenin from the coelomic fluid of the earthworm Eisenia fetida belongs to the aerolysin family of small beta-pore-forming toxins (beta-PFTs), some members of which are pathogenic to humans and animals. Despite efforts, a high-resolution structure of a channel for this family of proteins has been elusive and therefore the mechanism of activation and membrane insertion remains unclear. Here we determine the pore structure of lysenin by single particle cryo-EM, to 3.1 A resolution. The nonameric assembly reveals a long beta-barrel channel spanning the length of the complex that, unexpectedly, includes the two pre-insertion strands flanking the hypothetical membrane-insertion loop. Examination of other members of the aerolysin family reveals high structural preservation in this region, indicating that the membrane-insertion pathway in this family is conserved. For some toxins, proteolytic activation and pro-peptide removal will facilitate unfolding of the pre-insertion strands, allowing them to form the beta-barrel of the channel.
Cryo-EM structure of lysenin pore elucidates membrane insertion by an aerolysin family protein.,Bokori-Brown M, Martin TG, Naylor CE, Basak AK, Titball RW, Savva CG Nat Commun. 2016 Apr 6;7:11293. doi: 10.1038/ncomms11293. PMID:27048994[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kobayashi H, Sekizawa Y, Aizu M, Umeda M. Lethal and non-lethal responses of spermatozoa from a wide variety of vertebrates and invertebrates to lysenin, a protein from the coelomic fluid of the earthworm Eisenia foetida. J Exp Zool. 2000 Apr 1;286(5):538-49. PMID:10684578
- ↑ Yamaji-Hasegawa A, Makino A, Baba T, Senoh Y, Kimura-Suda H, Sato SB, Terada N, Ohno S, Kiyokawa E, Umeda M, Kobayashi T. Oligomerization and pore formation of a sphingomyelin-specific toxin, lysenin. J Biol Chem. 2003 Jun 20;278(25):22762-70. Epub 2003 Apr 3. PMID:12676961 doi:http://dx.doi.org/10.1074/jbc.M213209200
- ↑ Kiyokawa E, Makino A, Ishii K, Otsuka N, Yamaji-Hasegawa A, Kobayashi T. Recognition of sphingomyelin by lysenin and lysenin-related proteins. Biochemistry. 2004 Aug 3;43(30):9766-73. PMID:15274631 doi:http://dx.doi.org/10.1021/bi049561j
- ↑ Kobayashi H, Suzuki H, Ohta N. Exfoliation of the epidermal cells and defecation by amphibian larvae in response to coelomic fluid and lysenin from the earthworm Eisenia foetida. Biomed Res. 2006 Aug;27(4):169-81. PMID:16971770
- ↑ Sekizawa Y, Kubo T, Kobayashi H, Nakajima T, Natori S. Molecular cloning of cDNA for lysenin, a novel protein in the earthworm Eisenia foetida that causes contraction of rat vascular smooth muscle. Gene. 1997 May 20;191(1):97-102. PMID:9210594
- ↑ Yamaji A, Sekizawa Y, Emoto K, Sakuraba H, Inoue K, Kobayashi H, Umeda M. Lysenin, a novel sphingomyelin-specific binding protein. J Biol Chem. 1998 Feb 27;273(9):5300-6. PMID:9478988
- ↑ Bokori-Brown M, Martin TG, Naylor CE, Basak AK, Titball RW, Savva CG. Cryo-EM structure of lysenin pore elucidates membrane insertion by an aerolysin family protein. Nat Commun. 2016 Apr 6;7:11293. doi: 10.1038/ncomms11293. PMID:27048994 doi:http://dx.doi.org/10.1038/ncomms11293
|
