High resolution crystallographic studies of α-hemolysin-phospholipid complexes define heptamer-lipid head group interactions:: Implication for understanding protein-lipid interactions
High resolution crystallographic studies of α-hemolysin-phospholipid complexes define heptamer-lipid head group interactions:: Implication for understanding protein-lipid interactions
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DOI：
10.1110/ps.03561104
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发表时间：
2004-06-01
期刊：
影响因子：
8
通讯作者：
Gouaux, E
中科院分区：
文献类型：
--
作者：
Galdiero, S;Gouaux, E
α-溶血素是典型的成孔蛋白，其作为水溶性单体从金黄色葡萄球菌分泌。当单体与易感细胞的膜结合时，膜结合分子组装成裂解性七聚体。尽管双层或类双层环境对于毒素组装至关重要，但目前还没有关于毒素-磷脂复合物的高分辨率信息。我们在110 K和1.75-1.80埃的分辨率下测定了与甘油磷酸胆碱或二丙酰甘油磷酸胆碱结合的洗涤剂增溶的α-溶血素七聚体的结构。磷酸胆碱头部基团结合到边缘和stein结构域之间的缝隙中的每个亚基。季铵基团主要与芳族残基相互作用，而磷酸二酯部分与保守的精氨酸残基相互作用。这些结构为理解为什么α-溶血素优先在由磷酸胆碱脂质组成的膜上组装提供了分子基础。
The alpha-hemolysin is an archetypal pore-forming protein that is secreted from Staphylococcus aureus as a water-soluble monomer. When the monomer binds to the membrane of a Susceptible cell, the membrane-bound molecules assemble into the lytic heptamer. Although a bilayer or a bilayer-like environment are essential to toxin assembly, there is no high resolution information on toxin-phospholipid complexes. We have determined the structures of detergent-solubilized a-hemolysin heptamer bound to glycerophosphocholine or dipropanoyl glycerophosphocholine at 1.75-1.80 Angstrom resolution and 110 K. The phosphocholine head group binds to each subunit in a crevice between the rim and the stein domains. The quaternary ammonium group interacts primarily with aromatic residues, whereas the phosphodiester moiety interacts with a conserved arginine residue. These structures provide a molecular basis for understanding why alpha-hemolysin preferentially assembles on membranes comprised of phosphocholine lipids.