Small MscS-like mechanosensitive channels: understanding minimal requirements for structure and function

类似MSCS的小型机械敏感通道：了解结构和功能的最低要求

• 批准号: 538122946
• 负责人: Professorin Dr. Bettina Böttcher
• 金额: --
• 依托单位: Lehrstuhl für Biochemie I
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/538122946?language=en
• 关键词: Small; MscS; like; mechanosensitive; channels

Mechanosensitive channels are the molecular basis of many important biological processes. One function is the stress response to hypoosmotic shock, which is essential for the survival of single-celled organisms in direct contact with the environment. One of these channels is the mechanosensitive channel of small conductance of Escherichia coli (EcMscS). It is the best characterized member of the largest and most diverse family of mechanosensitive channels. EcMscS is considered to be the mechanistic core because most of the other members of the family are larger with additional N-terminal or C-terminal extensions. Here, we want to investigate the rare examples of MscS-like channels that are smaller than EcMscS. We have chosen three examples from different domains of life: one channel comes from the Archaea Candidatus woesearchaeota archaeon (CwMscS), one from the bacterium, Francisella tularensis (FtMscS) and another from the protozoan Trypanosomas cruzi (TcMscS). These channels lack either N-terminal regions that contribute to the voltage sensing, or a characteristic vestibule that provides stability and selectivity, or both. We want to know what functional effects the structural minimization has. To answer this question, we will determine the molecular structures of the three smaller MscS-like channels with electron cryo microscopy and quantify the functional properties with electrophysiology. We expect to unveil essential nuts and bolts of an ancient, bio-molecular machine that is widely distributed across all domains of life.

机械敏感通道是许多重要生物过程的分子基础。一种功能是对低渗休克的应激反应，这对与环境直接接触的单细胞生物体的生存至关重要。其中一个通道是大肠杆菌的小电导机械敏感通道(EcMscS)。它是最大和最多样化的机械敏感通道家族中特征最好的成员。EcMscS被认为是机械核心，因为该家族的大多数其他成员都较大，具有额外的N-末端或C-末端延伸。在这里，我们想要研究的是罕见的MSCs样通道，它们比ECMscs小。我们选择了三个来自不同生命领域的例子：一个渠道来自Archaea Candidatus woesearchaeota考古子(CwMscS)，一个来自细菌Francisella tularensis(FtMscS)，另一个来自原生动物锥虫(TcMscS)。这些通道要么缺乏有助于电压检测的N端区，要么缺乏提供稳定性和选择性的特征前庭，或者两者兼而有之。我们想知道结构最小化有什么功能效应。为了回答这个问题，我们将用电子冷冻显微镜确定三个较小的MSCs样通道的分子结构，并用电生理学来量化其功能特性。我们预计将揭开一台古老的生物分子机器的基本细节，这台机器广泛分布在生命的各个领域。