Liu Albert K, Pereira Jose H, Kehl Alexander J, Rosenberg Daniel J, Orr Douglas J, Chu Simon K S, Banda Douglas M, Hammel Michal, Adams Paul D, Siegel Justin B, Shih Patrick M
Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Sci Adv. 2022 Aug 26;8(34):eadc9440. doi: 10.1126/sciadv.adc9440.
Oligomerization is a core structural feature that defines the form and function of many proteins. Most proteins form molecular complexes; however, there remains a dearth of diversity-driven structural studies investigating the evolutionary trajectory of these assemblies. Ribulose-1,5-bisphosphate carboxylase-oxygenase (RuBisCO) is one such enzyme that adopts multiple assemblies, although the origins and distribution of its different oligomeric states remain cryptic. Here, we retrace the evolution of ancestral and extant form II RuBisCOs, revealing a complex and diverse history of oligomerization. We structurally characterize a newly discovered tetrameric RuBisCO, elucidating how solvent-exposed surfaces can readily adopt new interactions to interconvert or give rise to new oligomeric states. We further use these principles to engineer and demonstrate how changes in oligomerization can be mediated by relatively few mutations. Our findings yield insight into how structural plasticity may give rise to new oligomeric states.
寡聚化是一种核心结构特征，它定义了许多蛋白质的形式和功能。大多数蛋白质形成分子复合物；然而，缺乏基于多样性驱动的结构研究来探究这些组装体的进化轨迹。1,5-二磷酸核酮糖羧化酶/加氧酶（RuBisCO）就是这样一种采用多种组装形式的酶，尽管其不同寡聚状态的起源和分布仍不明确。在这里，我们追溯了祖先型和现存II型RuBisCO的进化历程，揭示了一段复杂多样的寡聚化历史。我们对新发现的四聚体RuBisCO进行了结构表征，阐明了溶剂暴露表面如何能够轻易地形成新的相互作用以相互转化或产生新的寡聚状态。我们进一步运用这些原理进行工程设计，并展示了相对较少的突变如何介导寡聚化的变化。我们的研究结果有助于深入了解结构可塑性如何产生新的寡聚状态。
