Structural landscape of the actin cytoskeleton
We are using cryo-EM to study the interfaces between diverse actin-binding proteins and actin filaments. Our studies support the concept that the actin structural landscape features conformations which are selectively recognized and / or induced by binding partners. This landscape could also be regulated by additional inputs (e.g. mechanical force or actin nucleotide state), providing a framework for establishing the local composition and architecture of subcellular cytoskeletal networks. Areas of interest include unconventional myosin motor proteins and cellular adhesion factors. We are also developing machine-learning based approaches for visualizing crosslinking proteins bridging filaments.

Cryo-EM maps of ADP and ADP-Pi F-actin with sufficient resolution to visualize bound water molecules. From Reynolds et al., Nature, 2022.

Atomistic models of T-plastin bridging actin filaments in two opposing orientations, from medium-resolution cryo-EM maps obtained through our machine-learning enabled processing pipeline. From Mei, Reynolds, et al., PNAS, 2022.

Cryo-EM structures show the adhesion proteins vinculin and α-catenin differentially engage actin through flexible C-terminal extensions. From Mei et al., Elife, 2020.