Dynamics of ATP-binding cassette contribute to allosteric control, nucleotide binding and energy transduction in ABC transporters.

Dynamics of ATP-binding cassette contribute to allosteric control, nucleotide binding and energy transduction in ABC transporters.
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ATP 结合盒的动力学有助于 ABC 转运蛋白的变构控制、核苷酸结合和能量转导。

DOI:
10.1016/j.jmb.2004.07.001
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发表时间:
2004
期刊:
Journal of molecular biology.
影响因子:
--
通讯作者:
Palmer,ArthurG
Palmer,ArthurG
中科院分区:
--
文献类型:
--
作者:
Wang,Chunyu;Karpowich,Nathan;Hunt,JohnF;Rance,Mark;Palmer,ArthurG

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三磷酸腺苷结合盒(ABC)转运体跨膜转运溶质,与囊性纤维化和多药耐药等重要疾病有关。这些分子机器由其特有的ABC模块提供能量,分子引擎由ATP水解提供燃料。对一个模型ABC,简氏甲烷球菌MJ1267的溶液核磁共振研究表明,腺苷二磷酸-镁结合改变了关键的ABC基序的灵活性,并诱导了LivG插入片段中构象动力学的变构变化,距离ATPase活性位点超过30Å。15N自旋驰豫数据支持核苷酸结合的“选择-匹配”模型。在ATP水解循环中,关键基序的刚性和灵活性之间的转换可能是ABC转运蛋白中机械力化学能量转导的关键。限制相关蛋白质的运动可能是变构通讯的中心机制。将核磁共振和X射线结晶学的动力学数据进行了比较,揭示了它们的总体一致性和互补性。
ATP-binding cassette (ABC) transporters move solutes across membranes and are associated with important diseases, including cystic fibrosis and multi-drug resistance. These molecular machines are energized by their charateristic ABC modules, molecular engines fuelled by ATP hydrolysis. A solution NMR study of a model ABC, Methanococcus jannaschii protein MJ1267, reveals that ADP-Mg binding alters the flexibilities of key ABC motifs and induces allosteric changes in conformational dynamics in the LivG insert, over 30Å away from the ATPase active site.15N spin relaxation data support a “selected-fit” model for nucleotide binding. Transitions between rigidity and flexibility in key motifs during the ATP hydrolysis cycle may be crucial to mechanochemical energy transduction in ABC transporters. The restriction of correlated protein motions is likely a central mechanism for allosteric communications. Comparison between dynamics data from NMR and X-ray crystallography reveals their overall consistency and complementarity.
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