Cryo-tides: synthetic peptides for cryo-EM grid preparation of multi-subunit protein complexes sensitive to the air-water interface

Authors

Alfieri, C., Young, R. V. C., McGeoch, A. J. S., Jessop, M., Greber, B. J.

Abstract

Cryogenic electron microscopy (cryo-EM) has enabled rapid progress in structural biology throughout the last decade. However, cryo-EM sample preparation still represents a major bottleneck in high-resolution structure determination. Many proteins and macromolecular complexes interact with the air-water interface during sample preparation, which can cause protein denaturation, complex disassembly, and preferred particle orientation. Development of methods to alleviate these issues is an active field of investigation. However, a universally applicable solution to this problem has not been found so far. Here, we describe the simple and cost-effective usage of synthetic peptides with defined amino acid sequence to protect cryo-EM samples from complex disassembly and reduce preferred orientation. We show benefits during cryo-EM grid preparation of a large E3 ubiquitin ligase termed the anaphase-promoting complex (APC/C), and the small CDK11:cyclin L:SAP30BP complex.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 02 Oct 2026.

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