Structural highlights
Function
NA1A_ANTXA Binds specifically to voltage-gated sodium channels (Nav) (site 3), thereby delaying their inactivation. This toxin retains the greatest capacity to discriminate between the cardiac (Nav1.5/SCN5A) and neuronal sodium channels (2.5 nM versus 120 nM, when electrophysiologically tested and 14 nM versus 400 nM, when tested by ion flux), whereas its paralog Anthopleurin-B has the highest affinity of all anemone toxins for the mammalian sodium channel (PubMed:13806, PubMed:7612595, PubMed:17092528). Its ability to differentiate between cardiac and skeletal channels appears to be associated with domain 4 of the channel (PubMed:9306007). This toxin does not slow or inhibit closed-state inactivation of cardiac sodium channels, but selectively modifies inactivation from the open-state (PubMed:8576699). It 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 (By similarity).[UniProtKB:P01531][1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Tanaka M, Hainu M, Yasunobu KT, Norton TR. Amino acid sequence of the Anthopleura xanthogrammica heart stimulant, anthopleurin A. Biochemistry. 1977 Jan 25;16(2):204-8. PMID:13806 doi:10.1021/bi00621a007
- ↑ Hanck DA, Sheets MF. Site-3 toxins and cardiac sodium channels. Toxicon. 2007 Feb;49(2):181-93. PMID:17092528 doi:10.1016/j.toxicon.2006.09.017
- ↑ Groome J, Lehmann-Horn F, Holzherr B. Open of a site-3 anemone toxin. Channels (Austin). 2011 Jan-Feb;5(1):65-78. PMID:21099342 doi:10.4161/chan.5.1.14031
- ↑ Hanck DA, Sheets MF. Modification of inactivation in cardiac sodium channels: ionic current studies with Anthopleurin-A toxin. J Gen Physiol. 1995 Oct;106(4):601-16. PMID:8576699 doi:10.1085/jgp.106.4.601
- ↑ 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