2mun | pdb_00002mun
Solution structure of mu-SLPTX3-Ssm6a
Structural highlights
FunctionTX32A_SCOMU Gating-modifier toxin that inhibits voltage-gated sodium channel with a preference for hNav1.7/SCN9A (IC(50)=25.4 nM) over hNav1.1/SCN1A (IC(50)=4.1 uM), hNav1.2/SCN2A (IC(50)=813 nM), and hNav1.6/SCN8A (IC(50)=15.2 uM) (PubMed:24082113). Is an effective analgesic in rodent pain models, since it is several-fold more effective than morphine in a rodent model of formalin-induced pain and is equipotent with morphine in its ability to reduce thermal and acid-induced pain (PubMed:24082113). In addition, this peptide shows a high level of resistance to proteases and a high thermal stability that may be explained by its predominant composition of alpha-helices (PubMed:24082113).[1] Publication Abstract from PubMedArthropod venoms consist primarily of peptide toxins that are injected into their prey with devastating consequences. Venom proteins are thought to be recruited from endogenous body proteins and mutated to yield neofunctionalized toxins with remarkable affinity for specific subtypes of ion channels and receptors. However, the evolutionary history of venom peptides remains poorly understood. Here we show that a neuropeptide hormone has been convergently recruited into the venom of spiders and centipedes and evolved into a highly stable toxin through divergent modification of the ancestral gene. High-resolution structures of representative hormone-derived toxins revealed they possess a unique structure and disulfide framework and that the key structural adaptation in weaponization of the ancestral hormone was loss of a C-terminal alpha helix, an adaptation that occurred independently in spiders and centipedes. Our results raise a new paradigm for toxin evolution and highlight the value of structural information in providing insight into protein evolution. Weaponization of a Hormone: Convergent Recruitment of Hyperglycemic Hormone into the Venom of Arthropod Predators.,Undheim EA, Grimm LL, Low CF, Morgenstern D, Herzig V, Zobel-Thropp P, Pineda SS, Habib R, Dziemborowicz S, Fry BG, Nicholson GM, Binford GJ, Mobli M, King GF Structure. 2015 Jun 2. pii: S0969-2126(15)00181-1. doi:, 10.1016/j.str.2015.05.003. PMID:26073605[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||
