化学
生物化学
细菌外膜
酶
磷脂酰肌醇
膜
细菌
膜蛋白
磷脂酶
生物物理学
信号转导
生物
大肠杆菌
基因
遗传学
作者
Mary F. Roberts,Khan Hm,Regensburg Goldstein,Nathalie Reuter,Anne Gershenson
出处
期刊:Chemical Reviews
[American Chemical Society]
日期:2018-08-27
卷期号:118 (18): 8435-8473
被引量:24
标识
DOI:10.1021/acs.chemrev.8b00208
摘要
Phosphatidylinositol-specific phospholipase C (PI-PLC) enzymes from Gram-positive bacteria are secreted virulence factors that aid in downregulating host immunity. These PI-PLCs are minimalist peripheral membrane enzymes with a distorted (βα)8 TIM barrel fold offering a conserved and stable scaffold for the conserved catalytic amino acids while membrane recognition is achieved mostly through variable loops. Decades of experimental and computational research on these enzymes have revealed the subtle interplay between molecular mechanisms of catalysis and membrane binding, leading to a semiquantitative model for how they find, bind, and cleave their respective substrates on host cell membranes. Variations in sequence and structure of their membrane binding sites may correlate with how enzymes from different Gram-positive bacteria search for their particular targets on the membrane. Detailed molecular characterization of protein-lipid interactions have been aided by cutting-edge methods ranging from 31P field-cycling NMR relaxometry to monitor protein-induced changes in phospholipid dynamics to molecular dynamics simulations to elucidate the roles of electrostatic and cation-π interactions in lipid binding to single molecule fluorescence measurements of dynamic interactions between PI-PLCs and vesicles. This toolkit is readily applicable to other peripheral membrane proteins including orthologues in Gram-negative bacteria and more recently discovered eukaryotic minimalist PI-PLCs.
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