Distinct Membrane Association Modes Facilitate Co-Translational Protein Targeting

Abstract

Deciphering the nature of protein interactions at the membrane surface is crucial to understanding the molecular mechanism, timing, and regulation of many essential cellular processes. The signal recognition particle (SRP) and its receptor (SR), which target the translating ribosomes to translocation machineries at the target membrane, provide an ideal model system for investigating the mechanism of membrane recruitment of protein machineries. Here we show that FtsY, the E. coli SR, interacts with the membrane through two distinct modes. Using single-molecule techniques that directly observe membrane association of FtsY in a supported lipid bilayer environment, we were able to detect and differentiate between the previously identified stable association mode as well as a transient interaction mode that is also crucial for targeting. Transition between these two modes is regulated by the SRP. Functional assays show that switching between transient and stabilized modes upon SRP binding is critical for successful targeting. We propose that, in contrast to currently accepted models in which FtsY is anchored on the membrane and awaits SRP encounter, this receptor rapidly cycles between cytosol and membrane and actively searches for cargo-loaded SRP. This active search could provide a mechanism to enhance efficient and accurate membrane localization of the targeting complex.

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