Melendez-Martinez David, Morales-Martinez Adriana, Almanza-Campos Iliana Vanessa, Sierra-Valdez Francisco, Borja Miguel, Carbajal-Saucedo Alejandro, Parkinson Christopher L, Benavides Jorge
Tecnologico de Monterrey, The Institute for Obesity Research, Ave. Eugenio Garza Sada 2501 Sur, Monterrey, N.L., 64700, Mexico.
Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Ave. Eugenio Garza Sada 2501 Sur, Monterrey, N.L., 64700, Mexico.
J Struct Biol X. 2025 May 27;11:100129. doi: 10.1016/j.yjsbx.2025.100129. eCollection 2025 Jun.
Snake venom defensins are a toxin family found in rattlesnake venoms () which are comprised of crotamine-like peptides and myotoxins. Their tertiary structure resembles the β-defensin family structure. Toxins from this family, such as crotamine () and myotoxin a (), have been described to generate paralysis through K 1.3 channel blockade, using three functional basic-hydrophobic dyads (Y-K, R-W, and R-W). However, the structural and functional properties of other snake venom defensins are scarcely described. For that reason, we evaluated the structural-functional characteristics of the rattlesnake venom defensins on the K 1.3 channel through analysis. 38 snake venom defensins were found to be peptides from 41 to 48 residues with a highly conserved sequence. The three-dimensional structures had great similitude (RMSD, <1.1 Å). Moreover, molecular dynamics simulations showed that the structures were stable (0.445 ± 0.23 nm). It was found that the snake venom defensins contain two or three basic-hydrophobic dyads, the first one is present in the N-terminal region of the defensin comprised by YK. The dyads two and three are contiguous, forming a motif in the γ-core, of which there are seven phenotypes: RWKW, RWRW, PWRR, PWKR, RWKR, RLGW, and GWRR. These dyads played a key role in the interaction of the defensins with the pore residues of the K1.3 channel. These results demonstrated that snake venom defensins have common structural and functional properties, interacting with the K 1.3 channel through the basic-hydrophobic dyads.
蛇毒防御素是一类存在于响尾蛇毒液中的毒素家族，由类巴曲酶肽和肌毒素组成。它们的三级结构类似于β-防御素家族结构。该家族的毒素，如巴曲酶和肌毒素a，已被描述通过使用三个功能性碱性-疏水性二元组（Y-K、R-W和R-W）阻断K1.3通道而导致麻痹。然而，其他蛇毒防御素的结构和功能特性鲜有描述。因此，我们通过分析评估了响尾蛇毒液防御素对K1.3通道的结构-功能特性。发现38种蛇毒防御素是由41至48个残基组成的肽，具有高度保守的序列。三维结构具有高度相似性（均方根偏差，<1.1 Å）。此外，分子动力学模拟表明这些结构是稳定的（0.445±0.23 nm）。研究发现蛇毒防御素含有两个或三个碱性-疏水性二元组，第一个存在于由YK组成的防御素N端区域。第二个和第三个二元组相邻，在γ-核心形成一个基序，共有七种表型：RWKW、RWRW、PWRR、PWKR、RWKR、RLGW和GWRR。这些二元组在防御素与K1.3通道孔残基的相互作用中起关键作用。这些结果表明蛇毒防御素具有共同的结构和功能特性，通过碱性-疏水性二元组与K1.3通道相互作用。
