Kutateladze T G, Overduin M
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Science. 2001 Mar 2;291(5509):1793-6. doi: 10.1126/science.291.5509.1793.
The recruitment of trafficking and signaling proteins to membranes containing phosphatidylinositol 3-phosphate [PtdIns(3)P] is mediated by FYVE domains. Here, the solution structure of the FYVE domain of the early endosome antigen 1 protein (EEA1) in the free state was compared with the structures of the domain complexed with PtdIns(3)P and mixed micelles. The multistep binding mechanism involved nonspecific insertion of a hydrophobic loop into the lipid bilayer, positioning and activating the binding pocket. Ligation of PtdIns(3)P then induced a global structural change, drawing the protein termini over the bound phosphoinositide by extension of a hinge. Specific recognition of the 3-phosphate was determined indirectly and directly by two clusters of conserved arginines.
包含磷脂酰肌醇3 - 磷酸[PtdIns(3)P]的膜上运输和信号蛋白的募集是由FYVE结构域介导的。在此，将早期内体抗原1蛋白（EEA1）的FYVE结构域在游离状态下的溶液结构与该结构域与PtdIns(3)P和混合胶束复合后的结构进行了比较。多步结合机制涉及一个疏水环非特异性插入脂质双层、定位并激活结合口袋。然后PtdIns(3)P的连接诱导了整体结构变化，通过一个铰链的延伸将蛋白质末端拉到结合的磷酸肌醇上。3 - 磷酸的特异性识别是由两组保守精氨酸间接和直接确定的。
