学术报告:In touch with the mechanosensitive Piezo channel: structure, ion permeation and mechanotransduction

2016/08/22 | 【 【打印】【关闭】 | 访问次数:

报告题目:In touch with the mechanosensitive Piezo channel: structure, ion permeation and mechanotransduction

报 告 人:肖百龙  研究员/青年千人(清华大学-北京大学生命科学联合中心)

报告时间:8月26日(周五)13:00

报告地点:嘉定园区学术活动中心307房间

报告简介:

Piezo proteins are evolutionarily conserved and functionally diverse mechanosensitive cation channels that play critical roles in various mechanotransduction processes. However, the overall structural architecture, ion permeation and gating mechanisms of Piezo channels have remained unknown. Here we determined the medium-resolution cryo-electron microscopy structure of the full-length (2,547 amino acids) mouse Piezo1 (Piezo1). Piezo1 forms a trimeric three-bladed, propeller-shaped structure with a putative central pore module that resembles the pore architecture of other trimeric channels such as the acid-sensing ion channel 1 (ASIC1), and peripheral regions composed of the extracellular ‘blade’ domains, ~12 apparently resolved peripheral helices (PHs) in each subunit and intracellular ‘beam’ and ‘anchor’ domains. Using chimeras, site-directed mutagenesis, and substituted cysteine accessibility method (SCAM), we functionally validated the miniature pore-forming module of Piezo1 that encodes the essential pore properties. We further identified the pore-lining helix and specific residues within the pore module that determine unitary conductance, pore blockage and ion selectivity for divalent and monovalent cations and anions. Remarkably, the non-pore-containing peripheral region of Piezo1 confers mechanosensitivity to ASIC1. Taken together, these data demonstrate that Piezo proteins consist of distinct and separable modules responsible for ion conduction and mechanical force sensing/transduction to co-ordinately fulfil their function as sophisticated mechanosensitive cation channels.

肖百龙简历.docx

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