Conserved conformational selection mechanism of Hsp70 chaperone-substrate interactions

• DOI: 10.7554/elife.32764
• Publication Date: 2018-02-20T12:50:28Z
• Authors: Ashok Sekhar; Algirdas Velyvis; Guy Zoltsman; Rina Rosenzweig; Guillaume Bouvignies; Lewis E Kay
• Keywords: Chaperone (clinical); Proteome; Structural Biology

Molecular recognition is integral to biological function and frequently involves preferred binding of a molecule one several exchanging ligand conformations in solution. In such process the bound structure can be selected from ensemble interconverting ligands priori (conformational selection, CS) or may form once (induced fit, IF). Here we focus on ubiquitous conserved Hsp70 chaperone which oversees integrity cellular proteome through its ATP-dependent interaction with client proteins. We directly quantify flux along CS IF pathways using solution NMR spectroscopy that exploits methyl TROSY effect selective isotope-labeling methodologies. Our measurements establish both bacterial human chaperones interact clients by selecting unfolded state pre-existing array structures, suggesting mode among Hsp70s highlighting importance molecular dynamics this event.