CryoSeek: A strategy for bioentity discovery using cryoelectron microscopy

• 成果类型: Article
• 署名作者: Wang, Tongtong; Li, Zhangqiang; Xu, Kui; Huang, Wenze; Huang, Gaoxingyu; Zhang, Qiangfeng Cliff; Yan, Nieng
• 署名单位: Tsinghua University; Westlake University; Westlake Laboratory; Shenzhen Medical Academy of Research & Translation (SMART); Shenzhen Bay Laboratory
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15112
• DOI: 10.1073/pnas.2417046121
• 发表日期: 2024-10-15
• 关键词: donor-strand exchange; nucleic-acids; protein; em; tools; MODEL

摘要

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- & Aring; 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 beta 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.