PT  - JOURNAL ARTICLE
AU  - Duccio Malinverni
AU  - Alfredo Jost Lopez
AU  - Paolo De Los Rios
AU  - Gerhard Hummer
AU  - Alessandro Barducci
TI  - Modeling Hsp70/Hsp40 interaction by multi-scale molecular simulations and co-evolutionary sequence analysis
AID  - 10.1101/067421
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 067421
4099  - http://biorxiv.org/content/early/2016/08/04/067421.short
4100  - http://biorxiv.org/content/early/2016/08/04/067421.full
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.