The Abundance of Phenylalanine in the DNAJB6b Linker Governs Its Role in Amyloid Suppression

Abstract

The molecular chaperone DNAJB6b inhibits the disease-related self-assembly of amyloid peptides in an efficient and ATP-independent manner. The molecular basis for this action is not yet fully understood, but the low-complexity region of DNAJB6b as a stand-alone peptide displays its antiamyloid formation properties and an ability to form self-assembled structures. Here, we studied the role of phenylalanine residues within the low-complexity region of the intact chaperone to gain insight into the role of these aromatic amino acid residues in chaperone-amyloid interactions. We designed, expressed, purified, and tested eight variants with various numbers of phenylalanine residues within the low-complexity region substituted with either alanine or serine. We show that substituting only 3 of these residues significantly affects the amyloid inhibition activity of the chaperone as well as its self-assembling ability, while substituting more residues affects these functions in a dose-dependent manner. Furthermore, we show that substituting all the phenylalanine residues within the low-complexity region reduces the amyloid inhibition activity of intact DNAJB6b to the equivalent of the isolated C-terminal domain, indicating that most of the chaperone activity stems from the aromatic residues within the low-complexity region.

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BibTeX RIS

BibTeX

@article{merkelis2026abundance,
  title = {{The Abundance of Phenylalanine in the DNAJB6b Linker Governs Its Role in Amyloid Suppression}},
  author = {Timas Merkelis and Erik Golovtchenko and Kalyani Sanagavarapu and Lovisa Björn and Cecilia Emanuelsson and Ulf Olsson and Sara Linse},
  journal = {ACS Omega},
  year = {2026},
  month = oct,
  doi = {10.1021/acsomega.6c07904},
  url = {https://pubs.acs.org/acsodf/article/11/41/63724/5444895/The-Abundance-of-Phenylalanine-in-the-DNAJB6b},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - The Abundance of Phenylalanine in the DNAJB6b Linker Governs Its Role in Amyloid Suppression
AU  - Timas Merkelis
AU  - Erik Golovtchenko
AU  - Kalyani Sanagavarapu
AU  - Lovisa Björn
AU  - Cecilia Emanuelsson
AU  - Ulf Olsson
AU  - Sara Linse
PY  - 2026
DA  - 2026/10/05
JO  - ACS Omega
DO  - 10.1021/acsomega.6c07904
UR  - https://pubs.acs.org/acsodf/article/11/41/63724/5444895/The-Abundance-of-Phenylalanine-in-the-DNAJB6b
AB  - The molecular chaperone DNAJB6b inhibits the disease-related self-assembly of amyloid peptides in an efficient and ATP-independent manner. The molecular basis for this action is not yet fully understood, but the low-complexity region of DNAJB6b as a stand-alone peptide displays its antiamyloid formation properties and an ability to form self-assembled structures. Here, we studied the role of phenylalanine residues within the low-complexity region of the intact chaperone to gain insight into the role of these aromatic amino acid residues in chaperone-amyloid interactions. We designed, expressed, purified, and tested eight variants with various numbers of phenylalanine residues within the low-complexity region substituted with either alanine or serine. We show that substituting only 3 of these residues significantly affects the amyloid inhibition activity of the chaperone as well as its self-assembling ability, while substituting more residues affects these functions in a dose-dependent manner. Furthermore, we show that substituting all the phenylalanine residues within the low-complexity region reduces the amyloid inhibition activity of intact DNAJB6b to the equivalent of the isolated C-terminal domain, indicating that most of the chaperone activity stems from the aromatic residues within the low-complexity region.
SN  - 2470-1343
ER  -

Abstract

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