2026-04-20 ジョージア工科大学（Georgia Tech）
＜関連情報＞
- https://research.gatech.edu/hidden-language-lifes-early-proteins
- https://www.cell.com/trends/chemistry/fulltext/S2589-5974(26)00047-X
折りたたみ可能性の境界領域：単純化されたタンパク質から学ぶ教訓 The borderlands of foldability: lessons from simplified proteins
Koh Seya (瀬谷巧) ∙ Alfie-Louise R. Brownless ∙ Shina C.L. Kamerlin ∙ Liam M. Longo
Trends in Chemistry Published:April 16, 2026
DOI:https://doi.org/10.1016/j.trechm.2026.03.001
Highlights
- Protein simplification studies identify folding-supportive environments, reveal connections between folds, and establish evidence-based limits for fold emergence.
- Symmetric folds can be formed by the homo-oligomerization of a 28- to 73-residue peptide. Simplification of ancient folds that lack rotational symmetry is still an unmet challenge.
- Diverse folds can be constructed with alphabets of just 7–14 amino acid types, including alphabets that lack aromatic amino acids and/or basic amino acids.
- Environment buffering—for example, by salts, chemical chaperones such as polyamines, or coacervates—could have supported the emergence of complex folds.
- Fold space is traversable, particularly among the small β-barrels and α/β folds.
Abstract
Proteins make complex life possible, yet our understanding of their emergence remains limited. What are the informational limits of protein folding, and how did the first proteins emerge? Protein simplification studies—in which contemporary folds are built from limited alphabets, symmetrized, fragmented, or shortened—have provided key insights into these questions. These studies use design constraints to address the discoverability of, and connectedness between, protein folds. By considering various environments, such as high salt concentrations or peptide–nucleic acid coacervates, the role of context in the emergence of folded domains is explored. Taken together, these studies support the early emergence of protein folds and reveal the existence of highly connected and readily traversable regions of sequence–structure space.
