Lipids modulate the increase of BK channel calcium sensitivity by the β1 subunit.
Lipids modulate the increase of BK channel calcium sensitivity by the β1 subunit.
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DOI：
10.1371/journal.pone.0107917
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Treistman SN
中科院分区：
文献类型：
--
作者：
Yuan C;Velázquez-Marrero C;Bernardo A;Treistman SN
BK的辅助β1亚基与成孔α亚基的共表达显著改变了表观钙敏感性。BK对平滑肌钙敏感性增加的机制研究主要集中在β1与α相互作用的能量效应上。我们采用一种新的方法，探索钙敏感性的β1修饰是否反映了通道蛋白与周围脂质之间的相互作用改变。我们将hSlo BK α和BK α+β1通道重组为两组双层。一组包含POPE与POPS、POPG、POPA和POPC，其中酰基链的长度是恒定的，但表面电荷不同。第二类是DOPE与不同酰基链长的磷脂酰胆碱（PC）：C（14∶1）、C（18∶1）、C（22∶1）和C（24∶1）以及脑鞘磷脂（SPM）形成的一系列中性双层，其中表面电荷恒定，但双层厚度不同。由β1亚基引起的钙敏感性增加在带负电荷的脂质双层中得以保留，但在中性双层中则没有，表明β1对表观钙敏感性的修饰受膜脂质调节，需要膜中带负电荷的脂质。此外，β1的存在降低了PC 14∶1薄双层膜和含SPM厚双层膜的BK活性，而对PC 18∶1、PC 22∶1和PC 24∶1双层膜的BK活性无明显影响。这些数据表明，辅助β1亚基不仅通过直接的亚基-亚基相互作用，而且通过调节脂质-蛋白质相互作用来微调通道门控。
Co-expression of the auxiliary β1 subunit with the pore forming α subunit of BK dramatically alters apparent calcium sensitivity. Investigation of the mechanism underlying the increase in calcium sensitivity of BK in smooth muscle has concentrated on the energetic effect of β1′s interaction with α. We take a novel approach, exploring whether β1 modification of calcium sensitivity reflects altered interaction between the channel protein and surrounding lipids. We reconstituted hSlo BK α and BK α+β1 channels into two sets of bilayers. One set contained POPE with POPS, POPG, POPA and POPC, where the length of acyl chains is constant, but surface charge differs. The second set is a series of neutral bilayers formed from DOPE with phosphatidylcholines (PCs) of varying acyl chain lengths: C (14∶1), C (18∶1), C (22∶1) and C (24∶1), and with brain sphingomyelin (SPM), in which surface charge is constant, but bilayer thickness varies. The increase in calcium sensitivity caused by the β1 subunit was preserved in negatively charged lipid bilayers but not in neutral bilayers, indicating that modification of apparent Ca2+ sensitivity by β1 is modulated by membrane lipids, requiring negatively charged lipids in the membrane. Moreover, the presence of β1 reduces BK activity in thin bilayers of PC 14∶1 and thick bilayers containing SPM, but has no significant effect on activity of BK in PC 18∶1, PC 22∶1 and PC 24∶1 bilayers. These data suggest that auxiliary β1 subunits fine-tune channel gating not only through direct subunit-subunit interactions but also by modulating lipid-protein interactions.
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影响因子：
64.8
作者：
Hansen, Scott B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
影响因子：
3.5
作者：
Ahring, PK;Strobaek, D;Johansen, TE
通讯作者：
Johansen, TE
DOI：
10.1152/ajplung.00104.2006
发表时间：
2006-10-01
影响因子：
4.9
作者：
Semenov, Iurii;Wang, Bin;Brenner, Robert
通讯作者：
Brenner, Robert
DOI：
10.1073/pnas.0506653102
发表时间：
2005-10-11
影响因子：
11.1
作者：
Kittler, JT;Chen, GJ;Moss, SJ
通讯作者：
Moss, SJ
影响因子：
2.4
作者：
Connell, Robert J. O.;Yuan, Chunbo;Treistman, Steven N.
通讯作者：
Treistman, Steven N.