TY  - JOUR
A1  - Malinverni, Duccio
A1  - Jost Lopez, Alfredo
A1  - De Los Rios, Paolo
A1  - Hummer, Gerhard
A1  - Barducci, Alessandro
T1  - Modeling Hsp70/Hsp40 interaction by multi-scale molecular simulations and coevolutionary sequence analysis
T2  - eLife
N2  - 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 the interaction remain elusive and contrasting models have been proposed for the transient Hsp70/Hsp40 complexes. Here we combine molecular simulations based on both coarse-grained and atomistic models with coevolutionary sequence analysis to shed light on this problem by focusing on the bacterial DnaK/DnaJ system. The integration of these complementary approaches resulted in a novel structural model that rationalizes previous experimental observations. We identify an evolutionarily conserved interaction surface formed by helix II of the DnaJ J-domain and a structurally contiguous region of DnaK, involving lobe IIA of the nucleotide binding domain, the inter-domain linker, and the β-basket of the substrate binding domain.
KW  - heat shock protein
KW  - protein coevolution
KW  - molecular modeling
KW  - protein complex
KW  - transient interaction
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73680
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-736806
SN  - 2050-084X
VL  - 6
IS  - e23471
PB  - eLife Sciences Publications
CY  - Cambridge
ER  -