Detection of isolated protein-bound metal ions by single-particle cryo-STEM

Nadav Elad, Giuliano Bellapadrona, Lothar Houben, Irit Sagi, Michael Elbaum

Research output: Contribution to journalArticlepeer-review


Metal ions play essential roles in many aspects of biological chemistry. Detecting their presence and location in proteins and cells is important for understanding biological function. Conventional structural methods such as X-ray crystallography and cryo-transmission electron microscopy can identify metal atoms on protein only if the protein structure is solved to atomic resolution. We demonstrate here the detection of isolated atoms of Zn and Fe on ferritin, using cryogenic annular dark-field scanning transmission electron microscopy (cryo-STEM) coupled with single-particle 3D reconstructions. Zn atoms are found in a pattern that matches precisely their location at the ferroxidase sites determined earlier by X-ray crystallography. By contrast, the Fe distribution is smeared along an arc corresponding to the proposed path from the ferroxidase sites to the mineral nucleation sites along the twofold axes. In this case the single-particle reconstruction is interpreted as a probability distribution function based on the average of individual locations. These results establish conditions for detection of isolated metal atoms in the broader context of electron cryo-microscopy and tomography.

Original languageEnglish
Pages (from-to)11139-11144
Number of pages6
JournalProceedings Of The National Academy Of Sciences Of The United States Of America-Physical Sciences
Issue number42
StatePublished - 17 Oct 2017

All Science Journal Classification (ASJC) codes

  • General


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