| Structural highlights
Function
[CRVP1_NAJAT] Inhibits calcium-activated potassium channels (KCa1.1/KCNMA1), voltage-gated potassium channel Kv1.3/KCNA3, and the calcium release channel/ryanodine receptor (RyR). Binds specifically to type 1 RyR (RyR1) from skeletal muscle. Inhibit both the binding of ryanodine to RyR1, and RyR1's calcium-channel activity. Inhibits carbachol-induced muscle contraction and weakly blocks muscle contraction evoked by potassium.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Blocking effect and crystal structure of natrin toxin, a cysteine-rich secretory protein from Naja atra venom that targets the BKCa channel.,Wang J, Shen B, Guo M, Lou X, Duan Y, Cheng XP, Teng M, Niu L, Liu Q, Huang Q, Hao Q Biochemistry. 2005 Aug 2;44(30):10145-52. PMID:16042391[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chang LS, Liou JC, Lin SR, Cheng YC. Purification and characterization of Taiwan cobra venom proteins with weak toxicity. Toxicon. 2005 Jan;45(1):21-5. PMID:15581679 doi:10.1016/j.toxicon.2004.09.002
- ↑ Wang F, Li H, Liu MN, Song H, Han HM, Wang QL, Yin CC, Zhou YC, Qi Z, Shu YY, Lin ZJ, Jiang T. Structural and functional analysis of natrin, a venom protein that targets various ion channels. Biochem Biophys Res Commun. 2006 Dec 15;351(2):443-8. Epub 2006 Oct 20. PMID:17070778 doi:10.1016/j.bbrc.2006.10.067
- ↑ Zhou Q, Wang QL, Meng X, Shu Y, Jiang T, Wagenknecht T, Yin CC, Sui SF, Liu Z. Structural and functional characterization of ryanodine receptor-natrin toxin interaction. Biophys J. 2008 Nov 1;95(9):4289-99. doi: 10.1529/biophysj.108.137224. Epub 2008 , Jul 25. PMID:18658224 doi:10.1529/biophysj.108.137224
- ↑ Wang J, Shen B, Guo M, Lou X, Duan Y, Cheng XP, Teng M, Niu L, Liu Q, Huang Q, Hao Q. Blocking effect and crystal structure of natrin toxin, a cysteine-rich secretory protein from Naja atra venom that targets the BKCa channel. Biochemistry. 2005 Aug 2;44(30):10145-52. PMID:16042391 doi:10.1021/bi050614m
- ↑ Wang J, Shen B, Guo M, Lou X, Duan Y, Cheng XP, Teng M, Niu L, Liu Q, Huang Q, Hao Q. Blocking effect and crystal structure of natrin toxin, a cysteine-rich secretory protein from Naja atra venom that targets the BKCa channel. Biochemistry. 2005 Aug 2;44(30):10145-52. PMID:16042391 doi:10.1021/bi050614m
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