TRPV1中热失活的热环基础。

Guangyu Wang
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引用次数: 0

摘要

哺乳动物的瞬时受体电位香草素-1(TRPV1)在重复或恒定的热刺激下表现出温度依赖性失活。然而,潜在的结构因素或主题尚未解决。在该计算研究中,采用基于图论的网格热力学模型来揭示在TRPV1的3D结构中识别的与温度相关的非共价相互作用如何发展出具有拓扑网格的系统流体网格状网状网络,该拓扑网格被约束为热环。结果表明,TRPV1活性在43°C开始,在56°C达到峰值,在61°C结束,是由不同门控状态下三个最大网格的热诱发熔化引起的。当第二大格栅控制从56°C到61°C之间的打开状态的可逆失活时,较小的格栅控制从43°C到61C之间的预打开-关闭状态的另一个不可逆失活。因此,TRPV1的两种不同的失活途径可能参与哺乳动物对抗毒辣的保护机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Thermo-ring basis for heat unfolding-induced inactivation in TRPV1.

Thermo-ring basis for heat unfolding-induced inactivation in TRPV1.

Thermo-ring basis for heat unfolding-induced inactivation in TRPV1.

Thermo-ring basis for heat unfolding-induced inactivation in TRPV1.

Transient receptor potential vanilloid-1 (TRPV1) is a capsaicin receptor and employs the use-dependent desensitization to protect mammals from noxious heat damage in response to repeated or constant heat stimuli. However, the underlying structural factor or motif has not been resolved precisely. In this computational study, the graph theory-based grid thermodynamic model was used to reveal how the temperature-dependent noncovalent interactions as identified in the 3D structures of rat TRPV1 could develop a well-organized fluidic grid-like mesh network, featuring various topological grids constrained as the thermo-rings that range in size from the biggest to the smallest to govern distinct structural and functional traits of the channel in response to varying temperature degrees. Following the findings that the heat unfolding of three specific biggest grids, one in the closed state and two in the open state, was respectively responsible for the reversible activation at 43 °C and thermal inactivation from 56 °C to 61 °C, a random smaller grid was further identified for the irreversible inactivation and the relevant use-dependent desensitization from the pre-open closed state between 43 °C and 61 °C. Thus, these two distinct inactivation pathways of TRPV1 may be involved in protecting mammals against noxious heat damages.

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