One sequence encoding two structures Most proteins have stable, folded structures, but there are rare examples of metamorphic proteins that can switch between two different folds that may each have a different function. Dishman et al. investigated the evolution of XCL1, which is a member of the chemokine family that interconverts between the chemokine fold and a second, noncanonical fold that forms dimers. The authors used nuclear magnetic resonance spectroscopy to investigate the structures of inferred evolutionary ancestral sequences. Their results suggest that XCL1 evolved from an ancestor with the chemokine fold and then transitioned to prefer the noncanonical fold before reaching the modern-day metamorphic protein. Science, this issue p. 86 The human protein XCL1 evolved to switch between two completely different folds with different functions. 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.

中文翻译：

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变态蛋白折叠转换的进化

一个序列编码两种结构 大多数蛋白质都具有稳定的折叠结构，但很少有变态蛋白质的例子可以在两种不同的折叠之间切换，而每种折叠可能具有不同的功能。迪什曼等人。研究了 XCL1 的进化，XCL1 是趋化因子家族的成员，在趋化因子折叠和形成二聚体的第二个非规范折叠之间相互转换。作者使用核磁共振波谱研究了推断的进化祖先序列的结构。他们的结果表明，XCL1 从具有趋化因子折叠的祖先进化而来，然后在达到现代变态蛋白之前转变为更喜欢非规范折叠。科学，本期第 14 页。86 人类蛋白质 XCL1 进化为在具有不同功能的两个完全不同的折叠之间切换。变态蛋白质在不同折叠之间切换，违背蛋白质折叠范式。目前尚不清楚进化过程中折叠转换是如何发生的。通过祖先重建和核磁共振，我们研究了变态人类蛋白XCL1的进化，该蛋白具有两个不同功能的不同折叠，使其成为趋化因子家族中一个不寻常的成员，该家族的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。二聚体界面的进化、结构约束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态的进化。然后，XCL1 可能进化为优先填充非规范折叠，然后达到现代几乎相同的折叠数量。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的原理。