Modeling the structural and dynamical changes of the epithelial calcium channel TRPV5 caused by the A563T variation based on the structure of TRPV6.
Modeling the structural and dynamical changes of the epithelial calcium channel TRPV5 caused by the A563T variation based on the structure of TRPV6.
复制标题
模拟由A563T变化引起的上皮钙通道TRPV5的结构和动态变化，该变化基于TRPV6的结构。
DOI：
10.1080/07391102.2018.1518790
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发表时间：
2019-08
影响因子：
4.4
通讯作者：
Peng JB
中科院分区：
文献类型：
--
作者：
Wang L;Holmes RP;Peng JB
TRPV5是一种上皮钙通道，在肾脏的活性钙重吸收过程中起关键作用。TRPV5基因中的单核苷酸多态性（SNP）rs4252499导致TRPV5的第六跨膜（TM）结构域中的A563T变异。我们以前的研究表明，这种变化增加了TRPV 5的Ca 2+转运功能。为了理解TRPV5的分子机制，基于TRPV6的新沉积结构建立了TRPV5的模型，TRPV6与TRPV5在建模区域中具有83.1%的氨基酸同一性。进行计算模拟以研究TRPV5变体与A563和T563之间的结构和动力学差异。与基于TRPV 1的模拟一致，结果表明A563T变异增加了残基563和V540之间的接触，V540与Ca 2+选择性过滤器中的关键残基D542相距一个残基。这种变化增强了孔区二级结构的稳定性，降低了563位残基周围残基的波动，减少了单体之间的相关和反相关运动。此外，该变化增加了选择性过滤器处的孔半径。这些发现通过基于最近确定的兔TRPV 5结构的模拟得到了证实。模拟结果为A563T变异引起TRPV5细胞内Ca2+内流增强提供了解释。A563T变异是一个有趣的例子，说明远离Ca2+选择性过滤器的残基如何影响TRPV 5通道的Ca2+转运功能。
TRPV5 is an epithelial Ca2+ channel that plays a key role in the active Ca2+ reabsorption process in the kidney. A single nucleotide polymorphism (SNP) rs4252499 in the TRPV5 gene results in an A563T variation in the sixth transmembrane (TM) domain of TRPV5. Our previous study indicated that this variation increases the Ca2+ transport function of TRPV5. To understand the molecular mechanism, a model of TRPV5 was established based on the newly deposited structure of TRPV6 that has 83.1% amino acid identity with TRPV5 in the modeled region. Computational simulations were performed to study the structural and dynamical differences between the TRPV5 variants with A563 and T563. Consistent with the TRPV1-based simulation, the results indicate that the A563T variation increases the contacts between residues 563 and V540, which is one residue away from the key residue D542 in the Ca2+-selective filter. The variation enhanced the stability of the secondary structure of the pore region, decreased the fluctuation of residues around residue 563, and reduced correlated and anti-correlated motion between monomers. Furthermore, the variation increases the pore radius at the selective filter. These findings were confirmed using simulations based on the recently determined structure of rabbit TRPV5. The simulation results provide an explanation for the observation of enhanced Ca2+ influx in TRPV5 caused by the A563T variation. The A563T variation is an interesting example of how a residue distant from the Ca2+-selective filter influences the Ca2+ transport function of the TRPV5 channel.
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影响因子：
9.8
作者：
Akey JM;Eberle MA;Rieder MJ;Carlson CS;Shriver MD;Nickerson DA;Kruglyak L
通讯作者：
Kruglyak L
影响因子：
8
作者：
COLOVOS, C;YEATES, TO
通讯作者：
YEATES, TO
DOI：
10.1152/ajprenal.90771.2008
发表时间：
2009-05-01
影响因子：
4.2
作者：
Na, Tao;Zhang, Wei;Peng, Ji-Bin
通讯作者：
Peng, Ji-Bin
影响因子：
4.4
作者：
ESSMANN, U;PERERA, L;PEDERSEN, LG
通讯作者：
PEDERSEN, LG
DOI：
10.1007/978-3-642-54215-2_13
发表时间：
2014-01-01
期刊：
MAMMALIAN TRANSIENT RECEPTOR POTENTIAL (TRP) CATION CHANNELS, VOL I
影响因子：
--
作者：
Na, Tao;Peng, Ji-Bin
通讯作者：
Peng, Ji-Bin