Cryo-EM reveals ArnA contamination during purification of a ciliary protein complex
Endogenous Escherichia coli proteins can co-purify with recombinant targets and dominate cryo-EM datasets, yet often escape detection during standard biochemical quality control. In parallel to the recent report by Caliseki and coworkers [Caliseki et al. (2025), Acta Cryst. D81, 545-557], we independently identified ArnA contamination while purifying a soluble, low-yield KIF17-IFT70 complex, ultimately obtaining a 3.23 Å resolution cryo-EM structure of ArnA rather than the intended target. Our results reinforce that ArnA enrichment reflects general features of His-tag affinity purification and can become particularly problematic in cryo-EM workflows when the intended target is low in yield or conformationally heterogeneous. By comparing biochemical behavior and cryo-EM outcomes, we outline why ArnA may evade SDS-PAGE and size-exclusion chromatography, and be underappreciated in routine mass spectrometry-based quality control, yet becomes structurally dominant in cryo-EM. These findings broaden the scope of the original study and highlight the need for early cryo-EM screening and improved contaminant awareness in structural biology.
Authors
- Masahide Kikkawa (ORCID: https://orcid.org/0000-0001-7656-8194)
- Xuguang Jiang (ORCID: https://orcid.org/0000-0001-7997-872X)
Institutions
- The University of Tokyo (JP)
Publication Details
- Journal
- Acta Crystallographica Section D Structural Biology
- Published
- 2026-04-10
- DOI
- https://doi.org/10.1107/s2059798326002846
- Primary Topic
- Advanced Electron Microscopy Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Japan Agency for Medical Research and Development
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency