title: Blocking effect and crystal structure of natrin toxin, a cysteine-rich secretory protein from Naja atra venom that targets the BKCa channel.
abstract: Cysteine-rich secretory proteins (CRISPs) are widespread in snake venoms. Some members of these CRISPs recently have been found to block L-type Ca(2+) channels or cyclic nucleotide-gated ion (CNG) channels. Here, natrin purified from Naja atra venom, a member of the CRISP family, can induce a further contractile response in the endothelium-denuded thoracic aorta of mouse which has been contracted by a high-K(+) solution. Further experiments show it can block the high-conductance calcium-activated potassium (BK(Ca)) channel in a concentration-dependent manner with an IC(50) of 34.4 nM and a Hill coefficient of 1.02, which suggests that only a single natrin molecule is required to bind an ion channel to block BK(Ca) current. The crystal structure of natrin displaying two domains in tandem shows its cysteine-rich domain (CRD) has relatively independent flexibility, especially for the C-terminal long loop (loop I) of CRD to participate in the interface of two domains. On the basis of previous studies of CNG channel and L-Ca(2+) channel blockers, and the sequence and structural comparison of natrin and stecrisp, the deviation of the vital loop I of CRD is suggested to contribute to different effects of some CRISPs in protein-protein interaction.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
authors.forename: Min
authors.initials: M
authors.lastname: Guo
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Lou
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Duan
authors.forename: Xin Ping
authors.initials: XP
authors.lastname: Cheng
authors.forename: Maikun
authors.initials: M
authors.lastname: Teng
authors.forename: Liwen
authors.initials: L
authors.lastname: Niu
authors.forename: Qun
authors.initials: Q
authors.lastname: Liu
authors.forename: Qingqiu
authors.initials: Q
authors.lastname: Huang
authors.forename: Quan
authors.initials: Q
authors.lastname: Hao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D003435:Crotalid Venoms / Q000737:chemistry; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry*; D051379:Mice; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000737:chemistry* / Q000633:toxicity; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D012996:Solutions
chemical_list: C486321:Crisp1 protein, mouse; D003435:Crotalid Venoms; D004546:Elapid Venoms; D008562:Membrane Glycoproteins; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D012996:Solutions; C495581:natrin protein, Naja atra; C495582:stecrisp protein, Trimeresurus stejnegeri; D003545:Cysteine