7JPM

The solution structure of omega-theraphotoxin-Pm1b isolated from King Baboon spider

7JPM の概要

• エントリーDOI: 10.2210/pdb7jpm/pdb
• NMR情報: BMRB: 30785
• 分子名称: Omega-theraphotoxin-Pm1b (1 entity in total)
• 機能のキーワード: inhibitor, cystein knot, voltage-gated sodium channel modulator, toxin
• 由来する生物種: Pelinobius muticus (king baboon spider)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4541.07

構造登録者

Chin, Y.K.-Y.,Ziegman, R.,Alewood, P.F. (登録日: 2020-08-09, 公開日: 2021-09-08, 最終更新日: 2024-10-23)

主引用文献

Finol-Urdaneta, R.K.,Ziegman, R.,Dekan, Z.,McArthur, J.R.,Heitmann, S.,Luna-Ramirez, K.,Tae, H.S.,Mueller, A.,Starobova, H.,Chin, Y.K.,Wingerd, J.S.,Undheim, E.A.B.,Cristofori-Armstrong, B.,Hill, A.P.,Herzig, V.,King, G.F.,Vetter, I.,Rash, L.D.,Adams, D.J.,Alewood, P.F.
Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider.
Proc.Natl.Acad.Sci.USA, 119:-, 2022

PubMed Abstract: The King Baboon spider, , is a burrowing African tarantula. Its impressive size and appealing coloration are tempered by reports describing severe localized pain, swelling, itchiness, and muscle cramping after accidental envenomation. Hyperalgesia is the most prominent symptom after bites from , but the molecular basis by which the venom induces pain is unknown. Proteotranscriptomic analysis of venom uncovered a cysteine-rich peptide, δ/κ-theraphotoxin-Pm1a (δ/κ-TRTX-Pm1a), that elicited nocifensive behavior when injected into mice. In small dorsal root ganglion neurons, synthetic δ/κ-TRTX-Pm1a (sPm1a) induced hyperexcitability by enhancing tetrodotoxin-resistant sodium currents, impairing repolarization and lowering the threshold of action potential firing, consistent with the severe pain associated with envenomation. The molecular mechanism of nociceptor sensitization by sPm1a involves multimodal actions over several ion channel targets, including Na1.8, K2.1, and tetrodotoxin-sensitive Na channels. The promiscuous targeting of peptides like δ/κ-TRTX-Pm1a may be an evolutionary adaptation in pain-inducing defensive venoms.

PubMed: 35074873
DOI: 10.1073/pnas.2110932119

実験手法

SOLUTION NMR