Department of Protein Structures, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Channels (Austin). 2012 Nov-Dec;6(6):479-82. doi: 10.4161/chan.22177. Epub 2012 Sep 18.
TRPM3 has been reported to play an important role in Ca(2+) homeostasis, but its gating mechanisms and regulation via Ca(2+) are unknown. Ca(2+) binding proteins such as calmodulin (CaM) could be probable modulators of this ion channel. We have shown that this protein binds to two independent domains, A35-K124 and H291-G382 on the TRPM3 N-terminus, which contain conserved hydrophobic as well as positively charged residues in specific positions, and that these residues have a crucial impact on its binding. We also showed that the other Ca(2+) binding protein, S100A1, is able to bind to these regions and that CaM and S100A1 compete for these binding sites on the TRPM3 N-terminus. Moreover, our results suggest that another very important TRP channel activity modulator, PtdIns(4,5)P(2), interacts with the CaM/S100A1 binding sites on the TRPM3 N-terminus with high affinity.
TRPM3 被报道在 Ca(2+) 稳态中发挥重要作用,但它的门控机制及其通过 Ca(2+)的调节尚不清楚。钙结合蛋白,如钙调蛋白 (CaM),可能是这种离子通道的潜在调节剂。我们已经表明,这种蛋白结合到 TRPM3 N 端的两个独立结构域 A35-K124 和 H291-G382,这些结构域含有特定位置的保守疏水区和带正电荷的残基,这些残基对其结合有至关重要的影响。我们还表明,另一种 Ca(2+)结合蛋白 S100A1 能够结合到这些区域,并且 CaM 和 S100A1 竞争 TRPM3 N 端上的这些结合位点。此外,我们的结果表明,另一种非常重要的 TRP 通道活性调节剂,PtdIns(4,5)P(2),以高亲和力与 TRPM3 N 端的 CaM/S100A1 结合位点相互作用。