Modeling the Self-assembly of the Cellulosome Enzyme Complex
Modeling the Self-assembly of the Cellulosome Enzyme Complex
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DOI：
10.1074/jbc.m110.186031
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发表时间：
2011-02-18
影响因子：
4.8
通讯作者：
Crowley, Michael F.
中科院分区：
文献类型：
--
作者：
Bomble, Yannick J.;Beckham, Gregg T.;Crowley, Michael F.
大多数细菌使用游离酶来降解自然界中的植物细胞壁。然而，一些细菌采取了一种不同的策略，酶可以是自由的，也可以被拴在蛋白质支架上，形成一种称为纤维素体的复合体。对这些大分子复合体的结构和机理的研究是一个活跃的和正在进行的研究课题，目的是找到利用纤维素体提高生物质转化的方法。纤维素体形成的几种机制尚不清楚，包括纤维素体酶如何在支架蛋白上组装，以及是什么控制了自组装过程中产生的纤维素体的数量。在这里，我们提出了一个粗粒模型来研究纤维素体的自组装。该模型捕捉到了三种纤维体酶(Cel5B、CELS和CbhA)以及来自热细胞梭菌的支架蛋白(CIPA)的大部分物理特征。蛋白质的结构由珠子表示，珠子由约束连接，以模拟这些蛋白质的灵活性和形状。从一个大的模拟集合中，纤维素体酶复合体的组装被证明是由它们的形状和模块化决定的。多模酶CbhA在统计上比CELS或CEL5B更频繁地与支架蛋白结合。结合的增强归因于这种酶的灵活性质和多模块，在支架蛋白周围提供了更长的停留时间。对影响纤维素体组装过程的因素的表征可能使创造设计者的纤维素体的新策略成为可能。
Most bacteria use free enzymes to degrade plant cell walls in nature. However, some bacteria have adopted a different strategy wherein enzymes can either be free or tethered on a protein scaffold forming a complex called a cellulosome. The study of the structure and mechanism of these large macromolecular complexes is an active and ongoing research topic, with the goal of finding ways to improve biomass conversion using cellulosomes. Several mechanisms involved in cellulosome formation remain unknown, including how cellulosomal enzymes assemble on the scaffoldin and what governs the population of cellulosomes created during self-assembly. Here, we present a coarse-grained model to study the self-assembly of cellulosomes. The model captures most of the physical characteristics of three cellulosomal enzymes (Cel5B, CelS, and CbhA) and the scaffoldin (CipA) from Clostridium thermocellum. The protein structures are represented by beads connected by restraints to mimic the flexibility and shapes of these proteins. From a large simulation set, the assembly of cellulosomal enzyme complexes is shown to be dominated by their shape and modularity. The multimodular enzyme, CbhA, binds statistically more frequently to the scaffoldin than CelS or Cel5B. The enhanced binding is attributed to the flexible nature and multimodularity of this enzyme, providing a longer residence time around the scaffoldin. The characterization of the factors influencing the cellulosome assembly process may enable new strategies to create designers cellulosomes.