Biological complexity: protein folding creates life (Introduction)

by David Turell , Monday, February 01, 2021, 19:07 (1172 days ago) @ David Turell

More studies in miss-folding causes and controls:

https://www.sciencedaily.com/releases/2021/02/210201101531.htm

"It's commonly accepted that protein folding/misfolding are alternative reactions of unfolded proteins but the principles governing this remain unknown. Here, researchers describe a general concept that links protein folding and misfolding: protein folding and amyloid formation are separated by the supersaturation barrier of a denatured protein. Breakdown of this supersaturation barrier is required to shift the protein to the amyloid pathway, linking Anfinsen's intramolecular folding universe with the 'outer' intermolecular misfolding universe.

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"Summarizing their motivation for this work, senior author Masahiro Noji explains: "The thermodynamic hypothesis of protein folding, known as the 'Anfinsen's dogma' describes that the native structure of a protein represents a free energy minimum determined by the amino acid sequence. However, this is not consistent with the misfolding of globular proteins to form amyloid fibrils." Therefore, Yuji Goto and colleagues set out to explore the link between protein folding and misfolding.

"Although proteins perform their functions by folding to their native structures, as represented by Anfinsen's dogma, proteins often misfold to form amyloid fibrils, leading to amyloidosis. In their paper, the research team from Osaka University describe a general concept for the link between protein folding and misfolding.

"'The supersaturation barrier of a denatured protein separates protein folding and amyloid formation, and misfolding occurs when this barrier breaks down" corresponding author Yuji Goto says. "Our results show a clear link between correct protein folding, as defined by Anfinsen's dogma, and protein misfolding."

"Supersaturation can be observed throughout nature in the formation of crystals, including those involved in ice formation. Here, the team at Osaka University show that supersaturation is fundamental to correct protein folding. The supersaturation barrier represents a novel concept that will advance the field of protein folding and contribute to the development of therapeutic strategies to prevent and treat amyloidosis, including those involved in neurodegenerative diseases."

Comment: We are still learning about folding of proteins which is so crucial to maintaining life.