Hierarchical dynamics in allostery following ATP hydrolysis monitored by single molecule FRET measurements and MD simulations. Issue 9 (22nd January 2021)

• Record Type: Journal Article
• Authors: Wolf, Steffen; Sohmen, Benedikt; Hellenkamp, Björn; Thurn, Johann; Stock, Gerhard; Hugel, Thorsten
• Is Part Of: Chemical science. Volume 12:Issue 9(2021)
• Page Start: 3350
• Page End: 3359
• Publication Date: 2021-01-22
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d0sc06134d
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : We report on a study that combines advanced fluorescence methods with molecular dynamics simulations to cover timescales from nanoseconds to milliseconds for a large protein, the chaperone Hsp90. Abstract : We report on a study that combines advanced fluorescence methods with molecular dynamics (MD) simulations to cover timescales from nanoseconds to milliseconds for a large protein. This allows us to delineate how ATP hydrolysis in a protein causes allosteric changes at a distant protein binding site, using the chaperone Hsp90 as test system. The allosteric process occurs via hierarchical dynamics involving timescales from nano- to milliseconds and length scales from Ångstroms to several nanometers. We find that hydrolysis of one ATP is coupled to a conformational change of Arg380, which in turn passes structural information via the large M-domain α-helix to the whole protein. The resulting structural asymmetry in Hsp90 leads to the collapse of a central folding substrate binding site, causing the formation of a novel collapsed state (closed state B) that we characterise structurally. We presume that similar hierarchical mechanisms are fundamental for information transfer induced by ATP hydrolysis through many other proteins.