Cryo-tides: synthetic peptides for cryo-EM grid preparation of multi-subunit protein complexes sensitive to the air-water interface
- 1The Institute of Cancer Research
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.
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BibTeX
@misc{alfieri2026cryotides,
title = {{Cryo-tides: synthetic peptides for cryo-EM grid preparation of multi-subunit protein complexes sensitive to the air-water interface}},
author = {C. Alfieri and R. V. C. Young and A. J. S. McGeoch and M. Jessop and B. J. Greber},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.30.755610},
url = {https://www.biorxiv.org/content/10.64898/2026.09.30.755610v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Cryo-tides: synthetic peptides for cryo-EM grid preparation of multi-subunit protein complexes sensitive to the air-water interface
AU - C. Alfieri
AU - R. V. C. Young
AU - A. J. S. McGeoch
AU - M. Jessop
AU - B. J. Greber
PY - 2026
DA - 2026/09/30
PB - bioRxiv
DO - 10.64898/2026.09.30.755610
UR - https://www.biorxiv.org/content/10.64898/2026.09.30.755610v1
AB - 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.
ER -