2024年 新着論文 13 分子生命科学分野から論文が発表されました

Enzymatic and synthetic regulation of polypeptide folding

Chem Sci. 2024 Jan 26;15(7):2282-2299. doi: 10.1039/d3sc05781j. eCollection 2024 Feb 14.

Authors

Takahiro Muraoka  1   2 Masaki Okumura  3 Tomohide Saio  4

Affiliations

  • 1 Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology Koganei Tokyo 184-8588 Japan muraoka@go.tuat.ac.jp.
  • 2 Kanagawa Institute of Industrial Science and Technology (KISTEC) Kanagawa 243-0435 Japan.
  • 3 Frontier Research Institute for Interdisciplinary Sciences, Tohoku University Sendai Miyagi 980-8578 Japan okmasaki@tohoku.ac.jp.
  • 4 Division of Molecular Life Science, Institute of Advanced Medical Sciences, Tokushima University Tokushima 770-8503 Japan saio@tokushima-u.ac.jp.

Abstract

Proper folding is essential for the biological functions of all proteins. The folding process is intrinsically error-prone, and the misfolding of a polypeptide chain can cause the formation of toxic aggregates related to pathological outcomes such as neurodegenerative disease and diabetes. Chaperones and some enzymes are involved in the cellular proteostasis systems that assist polypeptide folding to diminish the risk of aggregation. Elucidating the molecular mechanisms of chaperones and related enzymes is important for understanding proteostasis systems and protein misfolding- and aggregation-related pathophysiology. Furthermore, mechanistic studies of chaperones and related enzymes provide important clues to designing chemical mimics, or chemical chaperones, that are potentially useful for recovering proteostasis activities as therapeutic approaches for treating and preventing protein misfolding-related diseases. In this Perspective, we provide a comprehensive overview of the latest understanding of the folding-promotion mechanisms by chaperones and oxidoreductases and recent progress in the development of chemical mimics that possess activities comparable to enzymes, followed by a discussion of future directions.

Conflict of interest statement

There are no conflicts of interest to declare.