The low complexity linker of DNAJB6b is key to its anti-amyloid function

Area of Science:

• Biochemistry
• Molecular Biology
• Neuroscience

Background:

• Neurodegenerative diseases like Alzheimer's and Parkinson's are linked to amyloid fibril formation.
• The DNAJB6b (JB6) chaperone protein inhibits this self-assembly process independently of ATP.

Purpose of the Study:

• To investigate the molecular basis of JB6's anti-amyloid activity.
• To understand the role of the JB6 linker region in amyloid suppression.

Main Methods:

• Studied an isolated 110-amino acid linker construct of JB6.
• Analyzed the linker's structure, aggregation behavior, and anti-amyloid activity.
• Compared the linker's properties to the full-length JB6 chaperone.

Main Results:

• The JB6 linker contains significant alpha-helix and beta-sheet content.
• The linker is an amyloid-like peptide that self-assembles into structures larger than those of the intact chaperone.
• The isolated linker inhibits Aβ42 and α-synuclein fibril formation but is less potent than full-length JB6.

Conclusions:

• JB6's domains likely solubilize the linker, increasing its effective concentration for potent amyloid suppression.
• The self-assembly behavior of the linker contributes to its anti-amyloid mechanism.
• Understanding the linker's role provides insights into neurodegenerative disease mechanisms.