Investigating the structural dynamics of the PIEZO1 channel activation and inactivation by coarse-grained modeling.

ABSTRACT: The PIEZO channels, a family of mechanosensitive channels in vertebrates, feature a fast activation by mechanical stimuli (eg, membrane tension) followed by a slower inactivation. Although a medium-resolution structure of the trimeric form of PIEZO1 was solved by cryo-electron microscopy (cryo-EM), key structural changes responsible for the channel activation and inactivation are still unknown. Toward decrypting the structural mechanism of the PIEZO1 activation and inactivation, we performed systematic coarse-grained modeling using an elastic network model and related modeling/analysis tools (ie, normal mode analysis, flexibility and hotspot analysis, correlation analysis, and cryo-EM-based hybrid modeling and flexible fitting). We identified four key motional modes that may drive the tens

SUBMITTER: Zheng W 

PROVIDER: S-EPMC5758363 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature