Jouirou Besma, Mouhat Stéphanie, Andreotti Nicolas, De Waard Michel, Sabatier Jean-Marc
Laboratoire d'Ingénierie des Protéines, Faculte de Medecine Secteur Nord, CNRS FRE 2738, Bd Pierre Dramard, 13916 Marseille, France.
Toxicon. 2004 Jun 15;43(8):909-14. doi: 10.1016/j.toxicon.2004.03.024.
Ion channel-acting toxins are mainly short peptides generally present in minute amounts in the venoms of diverse animal species such as scorpions, snakes, spiders, marine cone snails and sea anemones. Interestingly, these peptides have evolved over time on the basis of clearly distinct architectural motifs present throughout the animal kingdom, but display convergent molecular determinants and functional homologies. As a consequence of this conservation of some key determinants, it has also been evidenced that toxin targets display some common evolutionary origins. Indeed, these peptides often target ion channels and ligand-gated receptors, though other interacting molecules such as enzymes have been further evidenced. In this review, we provide an overview of some selected peptides from various animal species that act on specific K+ conducting voltage-gated ion channels. In particular, we emphasize our global analysis on the structural determinants of these molecules that are required for the recognition of a particular ion channel pore structure, a property that should be correlated to the blocking efficacy of the K+ efflux out of the cell during channel opening. A better understanding of these molecular determinants is valuable to better specify and derive useful peptide pharmacological properties.
离子通道作用毒素主要是短肽，通常以微量存在于各种动物物种的毒液中，如蝎子、蛇、蜘蛛、海洋芋螺和海葵。有趣的是，这些肽随着时间的推移，基于整个动物界存在的明显不同的结构基序而进化，但显示出趋同的分子决定因素和功能同源性。由于一些关键决定因素的这种保守性，也已证明毒素靶点显示出一些共同的进化起源。确实，这些肽通常靶向离子通道和配体门控受体，不过其他相互作用分子如酶也已得到进一步证实。在本综述中，我们概述了来自各种动物物种的一些作用于特定钾离子传导电压门控离子通道的选定肽。特别是，我们着重对这些分子的结构决定因素进行整体分析，这些决定因素是识别特定离子通道孔结构所必需的，这一特性应与通道开放期间钾离子从细胞外流的阻断效力相关。更好地理解这些分子决定因素对于更好地明确并推导有用的肽类药理特性很有价值。
