# Unique characteristics of the J-domain proximal regions of Hsp70 cochaperone Apj1 in prion propagation/elimination and its overlap with Sis1 function

## TL;DR

This study explores the unique roles of different regions in the Apj1 protein, showing how they affect prion propagation and elimination in yeast.

## Contribution

The study identifies specific Apj1 fragments responsible for distinct prion-related functions, revealing functional diversity among J-domain proteins.

## Key findings

- A 90-residue Apj1 fragment is sufficient for prion curing when Hsp104 is overexpressed.
- A 121-residue Apj1 fragment can sustain cell growth without Sis1 and maintain Sis1-dependent prions.
- J-domains from other JDPs can replace Sis1 functions but not Apj1's role in prion curing.

## Abstract

J-domain proteins (JDPs) are obligate cochaperones of Hsp70s. The Class A JDP Apj1 of the yeast cytosol has an unusually complex region between the N-terminal J-domain and the substrate binding region—often called the Grich or GF region in Class A and B JDPs because of its typical abundance of glycine. The N-terminal 161-residue Apj1 fragment is known to be sufficient for Apj1 function in prion curing, driven by the overexpression of Hsp104. Further analyzing the N-terminal segment of Apj1, we found that a 90-residue fragment that includes the 70-residue J-domain and the adjacent 12-residue glutamine/alanine (Q/A) segment is sufficient for curing. Furthermore, the 121-residue fragment that includes the Grich region was sufficient to not only sustain the growth of cells lacking the essential Class B JDP Sis1 but also enabled the maintenance of several prions normally dependent on Sis1 for propagation. A J-domain from another cytosolic JDP could substitute for the Sis1-related functions but not for Apj1 in prion curing. Together, these results separate the functions of JDPs in prion biology and underscore the diverse functionality of multi-domain cytosolic JDPs in yeast.