Solution structure of Jingzhaotoxin-III, a peptide toxin inhibiting both Nav1.5 and Kv2.1 channels.
Jingzhaotoxin-III (JZTX-III) is a peptide toxin isolated from the venom of the Chinese spider Chilobrachys jingzhao that inhibits Nav channels of rat cardiac myocytes by modifying voltage-dependent gating and also binds to Kv2.1 channel (Kd = 0.43 microM) with an action model similar to that of hanatoxin1 and SGTx1. The solution structure of JZTX-III was determined by (1)H 2D NMR method. The toxin adopts an ICK motif composed of three beta-strands connected by four turns. Structural comparison of JZTX-III with those of other ICK motif peptides shows that they all adopt a conserved surface profile, a hydrophobic patch surrounded by charged residues, which might be the crucial site for voltage-gating ion channel inhibition. Furthermore, the similar action model of JZTX-III affecting both Kv and Nav channels implies that JZTX-III recognized a conserved receptor within the voltage sensing domains, which is similar to that of hanatoxin1 binding to both Kv and Cav channels.
Liao
Zhi
Z
College of Life Sciences, Peking University, Beijing 100083, PR China.
Yuan
Chunhua
C
Peng
Kuan
K
Xiao
Yucheng
Y
Liang
Songping
S
D020816:Amino Acid Motifs; D000818:Animals; D001097:Arachnida / Q000378:metabolism*; D005260:Female; D057927:Hydrophobic and Hydrophilic Interactions; D015640:Ion Channel Gating / Q000187:drug effects; D008958:Models, Molecular; D062554:NAV1.5 Voltage-Gated Sodium Channel; D019906:Nuclear Magnetic Resonance, Biomolecular; D009865:Oocytes / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity*; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011487:Protein Conformation; D051381:Rats; D051669:Shab Potassium Channels / Q000037:antagonists & inhibitors*; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism*; D013111:Spider Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity*; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
C496991:Kcnb1 protein, rat; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010455:Peptides; D026902:Potassium Channel Blockers; C568322:Scn5a protein, rat; D051669:Shab Potassium Channels; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013111:Spider Venoms; C487820:jingzhaotoxin-III, Chilobrachys jingzhao