A model of voltage gating developed using the KvAP channel crystal structure

被引:31
作者
Shrivastava, IH [1 ]
Durell, SR [1 ]
Guy, HR [1 ]
机构
[1] NCI, Lab Expt & Computat Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1529/biophysj.104.040592
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Having inspected the crystal structure of the complete KvAP channel protein, we suspect that the voltage-sensing domain is too distorted to provide reliable information about its native tertiary structure or its interactions with the central pore-forming domain. On the other hand, a second crystal structure of the isolated voltage-sensing domain may well correspond to a native open conformation. We also observe that the paddle model of gating developed from these two structures is inconsistent with many experimental results, and suspect it to be energetically unrealistic. Here we show that the isolated voltage-sensing domain crystal structure can be docked onto the pore domain portion of the full-length KvAP crystal structure in an energetically favorable way to create a model of the open conformation. Using this as a starting point, we have developed rather conventional models of resting and transition conformations based on the helical screw mechanism for the transition from the open to the resting conformation. Our models are consistent with both theoretical considerations and experimental results.
引用
收藏
页码:2255 / 2270
页数:16
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