Mancheño J M, Gasset M, Lacadena J, Martínez del Pozo A, Oñaderra M, Gavilanes J G
Departamento de Bioquímica y Biología Molecular, Facultad de Química, Universidad Complutense, Madrid, Spain.
J Theor Biol. 1995 Feb 7;172(3):259-67. doi: 10.1006/jtbi.1995.0022.
Alpha-sarcin is a cytotoxic protein composed of a single polypeptide chain. This protein shows a significant degree of amino acid sequence similarity with a group of several phylogenetically related fungal ribonucleases. The leading member of such a group is ribonuclease T1. Three proteins of this group, ribonucleases T1, Ms and F1, are well known in terms of their crystal structures. These data have been used to propose a conformation for alpha-sarcin. The secondary structure of the cytotoxin would contain one alpha-helix segment as well as around six beta-strands and 14 beta-turns. The folding of these structural motifs is proposed by comparison with the three-dimensional structure of the three proteins from the ribonuclease T1 subfamily. The four longest beta-strands of alpha-sarcin would define an antiparallel beta-sheet structure resulting in a highly hydrophobic domain. The predicted folding for alpha-sarcin is discussed in terms of the ability of this protein to electrostatically and hydrophobically interact with phospholipid vesicles. The proposed conformation would explain how a highly polar protein, such as alpha-sarcin, can produce membrane destabilization resulting in protein translocation across lipid bilayers.
α-肌动蛋白是一种由单条多肽链组成的细胞毒性蛋白。该蛋白与一组在系统发育上相关的真菌核糖核酸酶显示出显著程度的氨基酸序列相似性。这一组中的主要成员是核糖核酸酶T1。该组中的三种蛋白质，即核糖核酸酶T1、Ms和F1，就其晶体结构而言是众所周知的。这些数据已被用于提出α-肌动蛋白的构象。细胞毒素的二级结构将包含一个α-螺旋段以及大约六个β-链和14个β-转角。通过与核糖核酸酶T1亚家族的三种蛋白质的三维结构进行比较，提出了这些结构基序的折叠方式。α-肌动蛋白的四条最长的β-链将定义一个反平行的β-片层结构，从而形成一个高度疏水的结构域。根据该蛋白与磷脂囊泡进行静电和疏水相互作用的能力，讨论了α-肌动蛋白预测的折叠方式。所提出的构象将解释像α-肌动蛋白这样的高度极性蛋白如何能够导致膜不稳定，从而使蛋白质跨脂质双层转运。
