Preprint / Version 1

High-throughput cryo-EM characterization and automated model building of glycofibrils via CryoSeek

This article is a preprint and has not been certified by peer review.

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High-throughput cryo-EM; Glycobiology; Model building; Database; Structural biology

Abstract

With CryoSeek, a structure-first paradigm for discovery, we have determined high resolution 3D structures of a number of glycofibrils, in which well-ordered glycans either form a thick shell coating various protein cores or constitute the entire fibril. To improve the throughput of CryoSeek, we hereby report two methods. The recursive bisection clustering (RBC) strategy has been designed to enable high-throughput cryo-EM data processing of fibrils. EModelG is an AI-facilitated algorithm for automated model building of glycans. Using the RBC method, we have established a high-throughput workflow for CryoSeek and have reconstructed 3D EM maps for hundreds of fibrils that can be automatically modelled in EModelG. Based on their molecular compositions and structural features, we tentatively proposed a unified nomenclature scheme for the fibrils discovered via CryoSeek. These structures will lay the foundation for decoding the principles of glycan folding. Furthermore, to adapt to the high volume of cryo-EM structures quickly obtained with the CryoSeek strategy, we have established a namesake database for data archiving and sharing.

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Posted

2025-11-20

How to Cite

Hu, M., Chen, S., Wang, T., Qin, L., Zhang, Q., Zhang, Y., Ge, Q., Chen, T., Li, M., Li, C., Xu, G., Gui, Q., Li, Z., & Yan, N. (2025). High-throughput cryo-EM characterization and automated model building of glycofibrils via CryoSeek. LangTaoSha Preprint Server. https://doi.org/10.65215/bkvrt910

Declaration of Competing Interests

The authors declare no competing interests to disclose.