Tongtong Wang, Zhangqiang Li, Kui Xu, Wenze Huang, Gaoxingyu Huang, Qiangfeng Cliff Zhang, Nieng Yan
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引用次数: 0
摘要
结构生物学正在经历从定向结构测定到以结构为导向发现以前未表征的生物实体的范式转变。我们采用冷冻电子显微镜(cryo-EM)分析了从清华荷花池采集的过滤水样。在此,我们报告了两种高度相似的螺旋状纤维的结构测定和表征,这两种纤维被命名为 TLP-1a 和 TLP-1b,每种纤维的直径约为 8 nm,隧道宽 15 Å。这些纤维是由相似的蛋白质原体组装而成的,其结构已方便地在 CryoNet 中自动建模。原体结构与任何可用的实验结构都不匹配,但与许多功能未知的预测结构具有相同的折叠。原体 n + 4 的氨基末端 β 链插入到原体 n 的一个裂隙中,以完成一个类似免疫球蛋白(Ig)的结构域。这种包装机制被称为供体链交换(DSE),已在几种细菌的柔毛组装中观察到,其中供体是原体 n + 1。尽管TLP-1a/b纤维的形状和厚度各不相同,但这种相似性表明TLP-1a/b纤维可能代表了未定性的细菌纤毛虫。我们的研究展示了结构生物学的一个新兴范例,即高分辨率结构测定先于并推动完全未知对象的鉴定和表征。
CryoSeek: A strategy for bioentity discovery using cryoelectron microscopy.
Structural biology is experiencing a paradigm shift from targeted structural determination to structure-guided discovery of previously uncharacterized bioentities. We employed cryoelectron microscopy (cryo-EM) to analyze filtered water samples collected from the Tsinghua Lotus Pond. Here, we report the structural determination and characterization of two highly similar helical fibrils, named TLP-1a and TLP-1b, each approximately 8 nm in diameter with a 15-Å wide tunnel. These fibrils are assembled from a similar protein protomer, whose structure was conveniently automodeled in CryoNet. The protomer structure does not match any available experimental structures, but shares the same fold as many predicted structures of unknown functions. The amino-terminal β strand of protomer n + 4 inserts into a cleft in protomer n to complete an immunoglobulin (Ig)-like domain. This packing mechanism, known as donor-strand exchange (DSE), has been observed in several bacterial pilus assemblies, wherein the donor is protomer n + 1. Despite distinct shape and thickness, this reminiscence suggests that TLP-1a/b fibrils may represent uncharacterized bacterial pili. Our study demonstrates an emerging paradigm in structural biology, where high-resolution structural determination precedes and drives the identification and characterization of completely unknown objects.
期刊介绍:
The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), serves as an authoritative source for high-impact, original research across the biological, physical, and social sciences. With a global scope, the journal welcomes submissions from researchers worldwide, making it an inclusive platform for advancing scientific knowledge.