Reply to 'Concerns with yeast mitochondrial ADP/ATP carrier's integrity in DPC' and 'Dynamics and interactions of AAC3 in DPC are not functionally relevant'.
Reply to 'Concerns with yeast mitochondrial ADP/ATP carrier's integrity in DPC' and 'Dynamics and interactions of AAC3 in DPC are not functionally relevant'.
复制标题
回复“对 DPC 中酵母线粒体 ADP/ATP 载体完整性的担忧”和“DPC 中 AAC3 的动力学和相互作用在功能上不相关”。
DOI：
10.1038/s41594-018-0126-5
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发表时间：
2018
影响因子：
16.8
通讯作者：
Chou,JamesJ
中科院分区：
文献类型：
--
作者：
Yang,Qin;Brüschweiler,Sven;Zhao,Linlin;Chou,JamesJ
库劳斯卡斯等人。 1 和 King 等人。 2 声称我们在 NSMB 研究中用于测量酵母 ADP/ATP 载体 (yAAC3) 微毫秒动态的蛋白质3 并不处于功能性、天然状态，因此数据没有生物学相关性。我们坚信，十二烷基磷酸胆碱 (DPC) 中的 yAAC3 虽然折叠不理想且无法生成配体 CATR 的天然解离常数 (Kd)，但仍处于可以提供与功能研究相关的定性信息的状态。从很多方面来说，去污剂溶解的膜蛋白都处于次优折叠状态。去污剂可能会松动结构，有效地使配体结合位点更加动态。即使结合位点轻微不稳定也会对 Kd 产生巨大影响。关键问题是，我们能否从用于 NMR 分析的 yAAC3 样本中学到任何有意义的东西？ NMR 允许直接 Kd 测量，但这并不意味着样品必须具有生理 Kd 才被认为适合结构研究。
Kurauskas et al. 1 and King et al. 2 claim that the protein we used to measure the microto millisecond dynamics of yeast ADP/ATP carrier (yAAC3) in our NSMB study3 was not in a functional, native state and thus the data have no biological relevance. We strongly believe that yAAC3 in dodecylphosphocholine (DPC), although suboptimally folded and unable to generate a native dissociation constant (Kd) for ligand CATR, is nevertheless in a state that can provide qualitative information that is relevant for functional investigations. A suboptimally folded state is in many ways expected for detergent-solubilized membrane proteins; the detergent could have loosened the structure, effectively making the ligand-binding site more dynamic. Even minor destabilization of the binding site can have a dramatic effect on Kd. The key question is, can we learn anything meaningful from the yAAC3 sample used for NMR analyses? NMR allows direct Kd measurements, but this does not mean that a sample must have physiological Kd to be considered suitable for structural investigations.