Reshaping of the conformational search of a protein by the chaperone trigger factor

Reshaping of the conformational search of a protein by the chaperone trigger factor Nature 500, 7460 (2013). doi:10.1038/nature12293 Authors: Alireza Mashaghi, Günter Kramer, Philipp Bechtluft, Beate Zachmann-Brand, Arnold J. M. Driessen, Bernd Bukau & Sander J. Tans Protein folding is often described as a search process, in which polypeptides explore different conformations to find their native structure. Molecular chaperones are known to improve folding yields by suppressing aggregation between polypeptides before this conformational search starts, as well as by rescuing misfolds after it ends. Although chaperones have long been speculated to also affect the conformational search itself—by reshaping the underlying folding landscape along the folding trajectory—direct experimental evidence has been scarce so far. In Escherichia coli, the general chaperone trigger factor (TF) could play such a role. TF has been shown to interact with nascent chains at the ribosome, with polypeptides released from the ribosome into the cytosol, and with fully folded proteins before their assembly into larger complexes. To investigate the effect of TF from E. coli on the conformational search of polypeptides to their native state, we investigated individual maltose binding protein (MBP) molecules using optical tweezers. Here we show that TF binds folded structures smaller than one domain, which are then stable for seconds and u...
Source: Nature - Category: Research Authors: Tags: Letter Source Type: research