Keio University Human Biology-Microbiome-Quantum Research Center (WPI-Bio2Q) will hold a seminar as follows.
This is an event for faculty, students, and staff of Keio University.

In the eukaryotic cell, the endoplasmic reticulum (ER) is a specialized compartment for protein folding and maturation. Efficient ER functioning relies on a network of chaperones, calcium level and redox state, whereas variation in these cellular parameters can lead to ER stress and diseases. Here, we present structural and functional studies to resolve key mechanisms underlying the dynamic chaperone network at atomic resolution.
In a first step, we introduce in cyclo NMR to resolve the complete functional cycle of an ATP-driven molecular machine at atomic level. We create a non-equilibrium steady-state under turnover conditions inside the NMR tube, resolving all significantly populated states, their structures, mechanisms and kinetics connecting them, and the dynamic interplay with co-chaperones. The data resolve that the Hsp70 chaperone BiP undergoes a branched functional cycle comprised of seven states that is regulated by two autoinhibition switches.
In a second step, we characterize the disulfide isomerase PDIA6. We find that PDIA6 forms biomolecular condensates, both in vitro and in the ER lumen during protein folding homeostasis. Two specific interfaces in PDIA6 create the multivalency required for the condensate formation, which are dynamically regulated by calcium concentration. PDIA6 condensates recruit Hsp70 BiP and a number of further chaperones specifically into the condensates to form functional “folding factories” inside the ER. Together, our data establish the existence of a functional chaperone condensate that subcompartmentalizes the ER.