Trettel Daniel S, López Cesar A, Rodriguez Eliana, Marrone Babetta L, Gonzalez-Esquer Cesar Raul
Los Alamos National Laboratory, Bioscience Division, Microbial and Biome Sciences Group, Los Alamos, NM, USA.
Los Alamos National Laboratory, Theoretical Biology and Biophysics Group, Los Alamos, NM, USA.
Nat Commun. 2025 Aug 11;16(1):7378. doi: 10.1038/s41467-025-62772-0.
Bacterial microcompartments are protein organelles with diverse metabolic capabilities. Their functional diversity is determined by an enzymatic core that is sequestered within a structurally conserved protein shell architecture. Segregation of protein cargo into the bacterial microcompartment is enabled by encapsulation peptides, which are short helical domains fused to core proteins through a disordered linker. Here, we investigate how encapsulation peptides drive multicomponent cargo assembly into biomolecular condensates. In vitro experiments supported by molecular dynamics simulations demonstrate the importance of both conserved hydrophobic packing and electrostatic interactions in stabilizing trimeric encapsulation peptide bundles. Topological rearrangements of encapsulation peptide domains can drive programmable liquid- or gel-like partitioning in vitro and in vivo. This partitioning is found to be encapsulation peptide-specific, modular, and can co-assemble at least three fluorescent reporters. In summary, we describe the molecular features necessary to drive biomolecular condensation using a widespread peptide tag. This work can serve as a blueprint for implementing encapsulation peptide biotechnology across diverse applications.
细菌微区室是具有多种代谢能力的蛋白质细胞器。它们的功能多样性由隔离在结构保守的蛋白质外壳结构内的酶核心决定。通过包封肽可将蛋白质货物隔离到细菌微区室中，包封肽是通过无序连接子与核心蛋白融合的短螺旋结构域。在这里，我们研究包封肽如何驱动多组分货物组装成生物分子凝聚物。分子动力学模拟支持的体外实验证明了保守的疏水堆积和静电相互作用在稳定三聚体包封肽束中的重要性。包封肽结构域的拓扑重排可在体外和体内驱动可编程的液体或凝胶状分区。发现这种分区具有包封肽特异性、模块化，并且可以共同组装至少三种荧光报告分子。总之，我们描述了使用广泛存在的肽标签驱动生物分子凝聚所需的分子特征。这项工作可以作为在各种应用中实施包封肽生物技术的蓝图。
