美国威斯康星医学院Brian F. Volkman研究组组近日取得一项新成果。他们揭示变形蛋白中折叠转换的进化。该研究于2021年1月1日发表于《科学》杂志。

通过祖先重建和核磁共振，他们研究了变形人蛋白XCL1的进化，该蛋白具有两个具有不同功能的不同折叠，使其成为趋化因子家族中罕见成员，其成员通常采用一个保守的折叠。XCL1从具有趋化因子折叠的祖先进化而来。二聚体界面的演变、结构限制和分子应变的变化以及分子内蛋白质接触的改变推动了变形的进化。

然后，XCL1可能进化为优先填充非经典折叠，直到达到其近乎相等的折叠总数。这些发现阐明了一个序列如何进化为编码多种结构，揭示了蛋白质设计和工程学的原理。

研究人员表示，变形蛋白在不同折叠之间切换，不同于经典蛋白质折叠。尚不清楚进化过程中折叠转换如何产生。

附：英文原文

Title: Evolution of fold switching in a metamorphic protein

Author: Acacia F. Dishman, Robert C. Tyler, Jamie C. Fox, Andrew B. Kleist, Kenneth E. Prehoda, M. Madan Babu, Francis C. Peterson, Brian F. Volkman

Issue&Volume: 2021/01/01

Abstract: Metamorphic proteins switch between different folds, defying the protein folding paradigm. It is unclear how fold switching arises during evolution. With ancestral reconstruction and nuclear magnetic resonance, we studied the evolution of the metamorphic human protein XCL1, which has two distinct folds with different functions, making it an unusual member of the chemokine family, whose members generally adopt one conserved fold. XCL1 evolved from an ancestor with the chemokine fold. Evolution of a dimer interface, changes in structural constraints and molecular strain, and alteration of intramolecular protein contacts drove the evolution of metamorphosis. Then, XCL1 likely evolved to preferentially populate the noncanonical fold before reaching its modern-day near-equal population of folds. These discoveries illuminate how one sequence has evolved to encode multiple structures, revealing principles for protein design and engineering.

DOI: 10.1126/science.abd8700

Source: https://science.sciencemag.org/content/371/6524/86