只有两种氨基酸对于细胞溶解毒素在膜表面识别胆固醇是必需的。
Only two amino acids are essential for cytolytic toxin recognition of cholesterol at the membrane surface.
机构信息
Department of Microbiology and Immunology, University of Oklahoma Sciences Center, Oklahoma City, OK 73104, USA.
出版信息
Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4341-6. doi: 10.1073/pnas.0911581107. Epub 2010 Feb 9.
Abstract
The recognition and binding of cholesterol is an important feature of many eukaryotic, viral, and prokaryotic proteins, but the molecular details of such interactions are understood only for a few proteins. The pore-forming cholesterol-dependent cytolysins (CDCs) contribute to the pathogenic mechanisms of a large number of Gram-positive bacteria. Cholesterol dependence of the CDC mechanism is a hallmark of these toxins, yet the identity of the CDC cholesterol recognition motif has remained elusive. A detailed analysis of membrane interactive structures at the tip of perfringolysin O (PFO) domain 4 reveals that a threonine-leucine pair mediates CDC recognition of and binding to membrane cholesterol. This motif is conserved in all known CDCs and conservative changes in its sequence or order are not well tolerated. Thus, the Thr-Leu pair constitutes a common structural basis for mediating CDC-cholesterol recognition and binding, and defines a unique paradigm for membrane cholesterol recognition by surface-binding proteins.
摘要
胆固醇的识别和结合是许多真核生物、病毒和原核生物蛋白质的一个重要特征，但这些相互作用的分子细节仅在少数几种蛋白质中得到理解。形成孔的胆固醇依赖性细胞溶素（CDC）有助于许多革兰氏阳性菌的致病机制。CDC 机制的胆固醇依赖性是这些毒素的标志，但 CDC 胆固醇识别基序的身份仍然难以捉摸。对产气荚膜梭菌溶细胞素 O（PFO）结构域 4 顶端的膜相互作用结构的详细分析表明，苏氨酸-亮氨酸对介导 CDC 对膜胆固醇的识别和结合。该模序在所有已知的 CDC 中都保守，其序列或顺序的保守变化不能很好地耐受。因此，苏氨酸-亮氨酸对构成了介导 CDC-胆固醇识别和结合的共同结构基础，并为表面结合蛋白介导的膜胆固醇识别定义了一个独特的范例。
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