8.B.9 The Triflin Toxin (Triflin or CRISP) Family
Triflin toxins, present in snake venom glands, block smooth muscle contraction elicited by high K+-induced depolarization, but not caffeine-stimulated contraction. It may target voltage-gated Ca2+ channels. The 3-d structure dimension at 2.4A resolution has been described (Shikamoto et al., 2005). A 39aa peptide, similar to the N-terminus of triflin, is the active Ca2+ blocker (Aoki et al., 2008). The 240 aa protein (with signal sequences) is homologous to proteases and protease inhibitiors. Another member of the CRISP or SCP family, helothemine, is a toxic peptide secreted by the beaded lizard. It blocks Ca2+-transporting rhanodine receptors.
SCP-like extracellular protein domains of the CRISP-like sub-family,include plant pathogenesis-related protein 1 (PR-1), CRISPs, mammalian cysteine-rich secretory proteins, which combine SCP with a C-terminal cysteine rich domain, and allergen 5 from vespid venom. Involvement of CRISP in response to pathogens, fertilization, and sperm maturation have been proposed. One member, Tex31 from the venom duct of Conus textile, has been shown to possess proteolytic activity sensitive to serine protease inhibitors. SCP has also been proposed to be a Ca+ chelating serine protease. The Ca+-chelating function would fit with various signaling processes that members of this family, such as the CRISPs, are involved in as supported by sequence and structural evidence of a conserved pocket containing two histidines and a glutamate. It also may explain how helothermine, a toxic peptide secreted by the beaded lizard, blocks Ca+transporting ryanodine receptors. One member, DE or CRISP-1, has been shown to mediate gamete fusion by binding to the egg surface; a sequence motif in the SCP domain plays a role in that binding (Sunagar et al. 2012).