Evaluation of Competing J domain:Hsp70 Complex Models in Light of Existing Mutational and NMR Data

TL;DR

This study compares two models of J domain:Hsp70 complexes, demonstrating that the authors' previously published structure better explains mutational and NMR data and offers insights into the interaction mechanism.

Contribution

The paper provides a detailed analysis showing that the authors' existing J domain:Hsp70 complex model aligns better with experimental data than a recent alternative model.

Findings

Our structure better explains mutational data.

Our model aligns more closely with previous NMR studies.

The structure offers mechanistic insights into ATPase activation.

Abstract

Ahmad et al. recently presented an NMR-based model for a bacterial DnaJ J domain:DnaK(Hsp70):ADP complex(1) that differs significantly from the crystal structure of a disulfide linked mammalian auxilin J domain:Hsc70 complex that we previously published(2). They claimed that their model could better account for existing mutational data, was in better agreement with previous NMR studies, and that the presence of a cross-link in our structure made it irrelevant to understanding J:Hsp70 interactions. Here we detail extensive NMR and mutational data relevant to understanding J:Hsp70 function and show that, in fact, our structure is much better able to account for the mutational data and is in much better agreement with a previous NMR study of a mammalian polyoma virus T-ag J domain:Hsc70 complex than is the Ahmad et al. complex, and that our structure is predictive and provides insight into J:Hsp70 interactions and mechanism of ATPase activation.