Unveiling the cold reality of metamorphic proteins
成果类型：
Article
署名作者：
LiWang, Andy; Orban, John
署名单位：
University of California System; University of California Merced; University of California System; University of California Merced; University System of Maryland; Universities at Shady Grove; University of Maryland Baltimore; University System of Maryland; University of Maryland College Park
刊物名称：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN：
0027-9668
DOI：
10.1073/pnas.2422725122
发表日期：
2025-03-13
关键词：
摘要：
Metamorphic proteins switch reversibly between two differently folded states under a variety of environmental conditions. Their identification and prediction are gaining attention, but the fundamental physicochemical basis for fold switching remains poorly understood. In this Perspective article, we address this problem by surveying the landscape of well-characterized metamorphic proteins and noting that a significant fraction of them display temperature sensitivity. We then make the case that the dependence on temperature, in particular cold-denaturation effects, is likely to be an underlying property of many metamorphic proteins regardless of their ultimate triggering mechanisms, especially those with a single domain. The argument is supported by rigorous analysis of hydrophobic effects in each well-characterized metamorphic protein pair and a description of how these parameters relate to temperature. The conclusion discusses the relevance of these insights to a better understanding of prediction, evolution, and de novo design strategies for metamorphic proteins.