Emergence of fractal geometries in the evolution of a metabolic enzyme

• 成果类型: Article
• 署名作者: Sendker, Franziska L.; Lo, Yat Kei; Heimerl, Thomas; Bohn, Stefan; Persson, Louise J.; Mais, Christopher-Nils; Sadowska, Wiktoria; Paczia, Nicole; Nussbaum, Eva; Olmos, Maria del Carmen Sanchez; Forchhammer, Karl; Schindler, Daniel; Erb, Tobias J.; Benesch, Justin L. P.; Marklund, Erik G.; Bange, Gert; Schuller, Jan M.; Hochberg, Georg K. A.
• 署名单位: Max Planck Society; Philipps University Marburg; Uppsala University; Philipps University Marburg; University of Oxford; Max Planck Society; Eberhard Karls University of Tubingen; Max Planck Society; Philipps University Marburg; Max Planck Society
• 刊物名称: Nature
• ISSN/ISSBN: 0028-4415
• DOI: 10.1038/s41586-024-07287-2
• 发表日期: 2024-04-25
• 页码: 894-+
• 关键词: cryo-em; citrate synthase; phylogenetic analysis; sierpinski triangles; algorithms; symmetry; muscle; forms

摘要

Fractals are patterns that are self-similar across multiple length-scales(1). Macroscopic fractals are common in nature(2-4); however, so far, molecular assembly into fractals is restricted to synthetic systems(5-12). Here we report the discovery of a natural protein, citrate synthase from the cyanobacterium Synechococcus elongatus, which self-assembles into Sierpinski triangles. Using cryo-electron microscopy, we reveal how the fractal assembles from a hexameric building block. Although different stimuli modulate the formation of fractal complexes and these complexes can regulate the enzymatic activity of citrate synthase in vitro, the fractal may not serve a physiological function in vivo. We use ancestral sequence reconstruction to retrace how the citrate synthase fractal evolved from non-fractal precursors, and the results suggest it may have emerged as a harmless evolutionary accident. Our findings expand the space of possible protein complexes and demonstrate that intricate and regulatable assemblies can evolve in a single substitution.