Frontiers in Molecular Biosciences (Apr 2024)

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
https://doi.org/10.3389/fmolb.2024.1392608
Journal volume & issue
Vol. 11

Abstract

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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.

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