Nanomechanics of the substrate binding domain of Hsp70 determine its allosteric ATP-induced conformational change.
Proc Natl Acad Sci U S A
; 114(23): 6040-6045, 2017 06 06.
Article
em En
| MEDLINE
| ID: mdl-28533394
Owing to the cooperativity of protein structures, it is often almost impossible to identify independent subunits, flexible regions, or hinges simply by visual inspection of static snapshots. Here, we use single-molecule force experiments and simulations to apply tension across the substrate binding domain (SBD) of heat shock protein 70 (Hsp70) to pinpoint mechanical units and flexible hinges. The SBD consists of two nanomechanical units matching 3D structural parts, called the α- and ß-subdomain. We identified a flexible region within the rigid ß-subdomain that gives way under load, thus opening up the α/ß interface. In exactly this region, structural changes occur in the ATP-induced opening of Hsp70 to allow substrate exchange. Our results show that the SBD's ability to undergo large conformational changes is already encoded by passive mechanics of the individual elements.
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MEDLINE
Assunto principal:
Trifosfato de Adenosina
/
Proteínas de Choque Térmico HSP70
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article