Molecular diversity and evolution of cystine knot toxins of the tarantula Chilobrachys jingzhao

被引:61
作者
Chen, J. [1 ]
Deng, M. [1 ]
He, Q. [1 ]
Meng, E. [1 ]
Jiang, L. [1 ]
Liao, Z. [1 ]
Rong, M. [1 ]
Liang, S. [1 ]
机构
[1] Hunan Normal Univ, Key Lab Prot Chem & Dev Biol, Minist Educ, Coll Life Sci, Changsha 410081, Hunan, Peoples R China
关键词
toxin; molecular diversity; classification; pore-blocking; gating modifier; evolution;
D O I
10.1007/s00018-008-8135-x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cystine knot toxins (CKTs) in spider venoms represent a rich source of novel ligands for varied ion channels. Here, we identified 95 novel putative CKT precursors by analyzing expressed sequence tags of the tarantula Chilobrachys jingzhao venom gland. Phylogenetics analyses revealed one orphan family and six families with sequence similarity to known toxins. To further investigate the relationships of their structures, functions and evolution, we assayed 10 representative toxins for their effect on ion channels, and performed structure model comparisons, evolution analysis and toxin distribution analysis. This study revealed two major types of CKTs: pore-blocking toxins and gating modifier toxins. A few blockers were observed with relatively high abundance and wide distribution, which may be a category of original toxins that block channels conserved in various preys with relatively high specificity. The gating modifier families contain advanced toxins, usually have many members and interact with diverse regulatory components of channels.
引用
收藏
页码:2431 / 2444
页数:14
相关论文
共 58 条
[1]  
ADAMS ME, 1993, MOL PHARMACOL, V44, P681
[2]   Solution structure of Phrixotoxin 1, a specific peptide inhibitor of Kv4 potassium channels from the venom of the theraphosid spider Phrixotrichus auratus [J].
Chagot, B ;
Escoubas, P ;
Villegas, E ;
Bernard, C ;
Ferrat, G ;
Corzo, G ;
Lazdunski, M ;
Darbon, H .
PROTEIN SCIENCE, 2004, 13 (05) :1197-1208
[3]   DNA sequence quality trimming and vector removal [J].
Chou, HH ;
Holmes, MH .
BIOINFORMATICS, 2001, 17 (12) :1093-1104
[4]   Isolation, synthesis and pharmacological characterization of δ-palutoxins IT, novel insecticidal toxins from the spider Paracoelotes luctuosus (Amaurobiidae) [J].
Corzo, G ;
Escoubas, P ;
Stankiewicz, M ;
Pelhate, M ;
Kristensen, CP ;
Nakajima, T .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2000, 267 (18) :5783-5795
[5]   Pharmacologically active spider peptide toxins [J].
Corzo, G ;
Escoubas, P .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2003, 60 (11) :2409-2426
[6]   Solution structure and alanine scan of a spider toxin that affects the activation of mammalian voltage-gated sodium channels [J].
Corzo, Gerardo ;
Sabo, Jennifer K. ;
Bosmans, Frank ;
Billen, Bert ;
Villegas, Elba ;
Tytgat, Jan ;
Norton, Raymond S. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (07) :4643-4652
[7]   The cystine knot motif in toxins and implications for drug design [J].
Craik, DJ ;
Daly, NL ;
Waine, C .
TOXICON, 2001, 39 (01) :43-60
[8]   Identification and molecular cloning of insecticidal toxins from the venom of the brown spider Loxosceles intermedia [J].
de Castro, CS ;
Silvestre, FG ;
Araújo, SC ;
Yazbeck, GD ;
Mangili, OC ;
Cruz, I ;
Chávez-Olórtegui, C ;
Kalapothakis, E .
TOXICON, 2004, 44 (03) :273-280
[9]  
DeLano W.L, 2002, The Pymol Molecular Graphics System Version 1.0
[10]   cDNA sequence analysis of seven peptide toxins from the spider Selenocosmia huwena [J].
Diao, JB ;
Lin, Y ;
Tang, JZ ;
Liang, SP .
TOXICON, 2003, 42 (07) :715-723