RT Journal Article
SR Electronic
T1 Modeling Hsp70/Hsp40 interaction by multi-scale molecular simulations and co-evolutionary sequence analysis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 067421
DO 10.1101/067421
A1 Duccio Malinverni
A1 Alfredo Jost Lopez
A1 Paolo De Los Rios
A1 Gerhard Hummer
A1 Alessandro Barducci
YR 2016
UL http://biorxiv.org/content/early/2016/08/04/067421.abstract
AB The interaction between the Heat Shock Proteins 70 and 40 is at the core of the ATPase regulation of the chaperone machinery that maintains protein homeostasis. However, the structural details of this fundamental interaction are still elusive and contrasting models have been proposed for the transient Hsp70/Hsp40 complexes. Here we combine molecular simulations based on both coarsegrained and atomistic models with co-evolutionary sequence analysis to shed light on this problem by focusing on the bacterial DnaK/DnaJ system. The integration of these complementary approaches resulted into a novel structural model that rationalizes previous experimental observations. We identify an evolutionary-conserved interaction surface formed by helix II of the DnaJ J-domain and a groove on lobe IIA of the DnaK nucleotide binding domain, involving the inter-domain linker.