Characterization of the part of N-terminal PIP2 binding site of the TRPM1 channel
Characterization of the part of N-terminal PIP2 binding site of the TRPM1 channel
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DOI：
10.1016/j.bpc.2015.10.005
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发表时间：
2015-12-01
影响因子：
3.8
通讯作者：
Bousova, Kristyna
中科院分区：
文献类型：
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作者：
Jirku, Michaela;Bumba, Ladislav;Bousova, Kristyna
瞬时受体电位褪黑抑素-1 （TRPM1）是一种钙离子通道，对光响应性视网膜双极细胞的去极化至关重要，但该通道的大多数生理功能和细胞作用仍知之甚少。大多数瞬时受体电位（TRP）通道通常由细胞内蛋白和其他信号分子调节。磷脂酰肌醇-4,5二磷酸（PIP2）是细胞膜的一种次要磷脂成分，先前已被证明可直接结合TRP通道并在调节受体功能中发挥独特作用。为了表征PIP2作为TRPM1的潜在调节因子的结合，我们利用生物物理方法和分子建模来研究PIP2与TRPM1 n端片段（残基A451-N566）的相互作用。TRPM1的碱性n端残基1（464）表明它是假定的pleckstrin同源（PH）结构域的一部分，并参与与PIP2的相互作用。这是第一个详细报道PIP2在TRPM1受体n端结合的报道。(C) 2015 Elsevier B.V.版权所有
Transient receptor potential melastatin-1 (TRPM1) is a calcium channel that is essential for the depolarization of photo-responsive retinal bipolar cells, but most of the physiological functions and cellular roles of this channel are still poorly understood. Most transient receptor potential (TRP) channels are typically regulated by intracellular proteins and other-signaling molecules. Phosphatidylinositol-4,5 bisphosphate (PIP2), a minor phospholipid component of cell membranes, has previously been shown to directly bind TRP channels and to play a unique role in modulating receptor function. To characterize the binding of PIP2 as a potential regulator of TRPM1, we utilized biophysical methods and molecular modeling to study the interactions of PIP2 with an N-terminal fragment of TRPM1 (residues A451-N566). The basic N-terminal residue 1(464 of TRPM1 suggests that it is part of putative pleckstrin homology (PH) domain and is involved in the interactions with PIP2. This is the first report detailing the binding of PIP2 at the N-terminus of the TRPM1 receptor. (C) 2015 Elsevier B.V. All rights reserved.