Laboratoire de Biophysique Statistique, Faculté de Sciences de Base, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
Gerhard Hummer
Max Planck Institute of Biophysics, Frankfurt am Main, Germany; Institut für Biophysik, Johann Wolfgang Goethe Universität Frankfurt, Frankfurt am Main, Germany
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 [Formula: see text]-basket of the substrate binding domain.
