6imf
From Proteopedia
Crystal structure of TOXIN/ANTITOXIN complex
Structural highlights
FunctionCRVP_PROFL Blocks contraction of smooth muscle elicited by high potassium-induced depolarization (PubMed:12047379). May target voltage-gated calcium channels (Cav) on smooth muscle.[1] Publication Abstract from PubMedVenomous snakes have endogenous proteins that neutralize the toxicity of their venom components. We previously identified five small serum proteins (SSP-1-SSP-5) from a highly venomous snake belonging to the family Viperidae as inhibitors of various toxins from snake venom. The endogenous inhibitors belong to the prostate secretory protein of 94 amino acids (PSP94) family. SSP-2 interacts with triflin, which is a member of the cysteine-rich secretory protein (CRISP) family that blocks smooth muscle contraction. However, the structural basis for the interaction and biological roles of these inhibitors is largely unknown. Here, we determined the crystal structure of the SSP-2-triflin complex at 2.3 A resolution. A concave region centrally located in the N-terminal domain of triflin is fully occupied by the terminal -strands of SSP-2. SSP-2 does not bind tightly to the C-terminal cysteine-rich domain of triflin; this domain is thought to be responsible for its channel-blocker function. Instead, the cysteine-rich domain is tilted 7.7 degrees upon binding to SSP-2, and the inhibitor appears to sterically hinder triflin binding to calcium channels. These results help explain how an endogenous inhibitor prevents the venomous protein from maintaining homeostasis in the host. Furthermore, this interaction also sheds light on the binding interface between the human homologues PSP94 and CRISP-3, which are upregulated in prostate and ovarian cancers. Crystal structure of the complex between venom toxin and serum inhibitor from viperidae snake.,Shioi N, Tadokoro T, Shioi S, Okabe Y, Matsubara H, Kita S, Ose T, Kuroki K, Terada S, Maenaka K J Biol Chem. 2018 Nov 30. pii: RA118.006840. doi: 10.1074/jbc.RA118.006840. PMID:30504218[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Large Structures | Protobothrops flavoviridis | Hu Y | Kita S | Kurahara LH | Kuroki K | Maenaka K | Matsubara H | Okabe Y | Ose T | Shioi N | Shioi S | Tadokoro T | Terada S