Structural highlights
Function
NA1B_ANTXA Binds specifically to voltage-gated sodium channels (Nav) (site 3), thereby delaying their inactivation. This toxin has the highest affinity of all anemone toxins for the mammalian sodium channel, whereas its paralog Anthopleurin-A retains the greatest capacity to discriminate between cardiac (Nav1.5/SCN5A) and neuronal sodium channels (PubMed:8916901). When tested electrophysiologically, this toxin exhibits a high affinity for multiple sodium channels with a 50-fold preference for rat cardiac (Nav1.5/SCN5A) over neuronal channels (0.1 nM versus 5 nM). When tested by ion flux, the affinities are similar and appear to have higher affinity (9 nM versus 22 nM) (PubMed:8276803, PubMed:7612595). The residue Lys-37 of this toxin has been shown to interact with channel Nav1.5 (residue Asp-1612 in rat and Asp-1610 in human), which is located in the DIV S3-S4 linker (corresponding to channel site 3) (PubMed:9417050, PubMed:24898004). Selectively modifies sodium channel inactivation from the open state with little effect on channel activation or on inactivation from closed states (By similarity). Does not display phospholipid-binding activities, suggesting that the domain IV S3-S4 linker is located at the extracellular surface and not buried in the phospholipid bilayer (PubMed:15632158).[UniProtKB:P01530][1] [2] [3] [4] [5] [6] [7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Smith JJ, Alphy S, Seibert AL, Blumenthal KM. Differential phospholipid binding by site 3 and site 4 toxins. Implications for structural variability between voltage-sensitive sodium channel domains. J Biol Chem. 2005 Mar 25;280(12):11127-33. PMID:15632158 doi:10.1074/jbc.M412552200
- ↑ Xiao Y, Blumenthal K, Cummins TR. Gating-pore currents demonstrate selective and specific modulation of individual sodium channel voltage-sensors by biological toxins. Mol Pharmacol. 2014 Aug;86(2):159-67. PMID:24898004 doi:10.1124/mol.114.092338
- ↑ Khera PK, Benzinger GR, Lipkind G, Drum CL, Hanck DA, Blumenthal KM. Multiple cationic residues of anthopleurin B that determine high affinity and channel isoform discrimination. Biochemistry. 1995 Jul 11;34(27):8533-41. PMID:7612595 doi:10.1021/bi00027a003
- ↑ Gallagher MJ, Blumenthal KM. Importance of the unique cationic residues arginine 12 and lysine 49 in the activity of the cardiotonic polypeptide anthopleurin B. J Biol Chem. 1994 Jan 7;269(1):254-9 PMID:8276803
- ↑ Kelso GJ, Drum CL, Hanck DA, Blumenthal KM. Role for Pro-13 in directing high-affinity binding of anthopleurin B to the voltage-sensitive sodium channel. Biochemistry. 1996 Nov 12;35(45):14157-64. PMID:8916901 doi:10.1021/bi961584d
- ↑ Benzinger GR, Drum CL, Chen LQ, Kallen RG, Hanck DA, Hanck D. Differences in the binding sites of two site-3 sodium channel toxins. Pflugers Arch. 1997 Nov;434(6):742-9. PMID:9306007 doi:10.1007/s004240050460
- ↑ Benzinger GR, Kyle JW, Blumenthal KM, Hanck DA. A specific interaction between the cardiac sodium channel and site-3 toxin anthopleurin B. J Biol Chem. 1998 Jan 2;273(1):80-4. PMID:9417050 doi:10.1074/jbc.273.1.80