2024Wang CryoSeek

Citation

Wang, T., Li, Z., Xu, K., Huang, W., Huang, G., Zhang, Q.C. and Yan, N. 2024. CryoSeek: A strategy for bioentity discovery using cryoelectron microscopy. Proceedings of the National Academy of Sciences. 121, 42 (2024), e2417046121.

Abstract

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.

Links

https://www.pnas.org/doi/abs/10.1073/pnas.2417046121