首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Calmodulin overexpression does not alter Cav1.2 function or oligomerization state
Abstract:Interactions between calmodulin (CaM) and voltage-gated calcium channels (Cavs) are crucial for Cav activity-dependent feedback modulation. We recently reported an X-ray structure that shows two Ca2+/CaM molecules bound to the Cav1.2 C terminal tail, one at the PreIQ region and one at the IQ domain. Surprisingly, the asymmetric unit of the crystal showed a dimer in which Ca2+/CaM bridged two PreIQ helixes to form a 4:2 Ca2+/CaM:Cav C-terminal tail assembly. Contrary to previous proposals based on a similar crystallographic dimer, extensive biochemical analysis together with subunit counting experiments of full-length channels in live cell membranes failed to find evidence for multimers that would be compatible with the 4:2 crossbridged complex. Here, we examine this possibility further. We find that CaM over-expression has no functional effect on Cav1.2 inactivation or on the stoichiometry of full-length Cav1.2. These data provide further support for the monomeric Cav1.2 stoichiometry. Analysis of the electrostatic surfaces of the 2:1 Ca2+/CaM:CaV C-terminal tail assembly reveals notable patches of electronegativity. These could influence various forms of channel modulation by interacting with positively charged elements from other intracellular channel domains.
Keywords:
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号