Single-molecule mechanical studies of chaperones and their clients.

Abstract

Single-molecule force spectroscopy provides access to the mechanics of biomolecules. Recently, magnetic and laser optical tweezers were applied in the studies of chaperones and their interaction with protein clients. Various aspects of the chaperone-client interactions can be revealed based on the mechanical probing strategies. First, when a chaperone is probed under load, one can examine the inner workings of the chaperone while it interacts with and works on the client protein. Second, when protein clients are probed under load, the action of chaperones on folding clients can be studied in great detail. Such client folding studies have given direct access to observing actions of chaperones in real-time, like foldase, unfoldase, and holdase activity. In this review, we introduce the various single molecule mechanical techniques and summarize recent single molecule mechanical studies on heat shock proteins, chaperone-mediated folding on the ribosome, SNARE folding, and studies of chaperones involved in the folding of membrane proteins. An outlook on significant future developments is given.