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

Samantha J Ganser; Bridget A McNish; Gillian L Schwanitz; John L Delaney; Bridget A Corpus; Brenda A Schilke; Anup K Biswal; Chandan Sahi; Elizabeth A Craig; Justin K Hines

doi:10.3389/fmolb.2024.1392608

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

Front Mol Biosci. 2024 Apr 24:11:1392608. doi: 10.3389/fmolb.2024.1392608. eCollection 2024.

Affiliations

¹ Department of Chemistry, Lafayette College, Easton, PA, United States.
² Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, United States.
³ Department of Biological Sciences, Indian Institute of Science Education and Research Bhopal, Bhopal, India.

^# Contributed equally.

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 G_rich 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 G_rich 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.

Keywords: Hsp104; Hsp40; J-protein; amyloid; chaperone.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Lafayette College Chemistry Department, the Henry Dreyfus Teacher Scholar Award Number TH-18-017 (to JH), the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R15 GM110606 (to JH), and R35 GM127009 (to EC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript; or in the decision to publish the results.