Subtomogram analysis: The sum of a tomogram's particles reveals molecular structure in situ

Friedrich Förster

doi:10.1016/j.yjsbx.2022.100063

Subtomogram analysis: The sum of a tomogram's particles reveals molecular structure in situ

Friedrich Förster

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Cryo-electron tomography is uniquely suited to provide insights into the molecular architecture of cells and tissue in the native state. While frozen hydrated specimens tolerate sufficient electron doses to distinguish different types of particles in a tomogram, the accumulating beam damage does not allow resolving their detailed molecular structure individually. Statistical methods for subtomogram averaging and classification that coherently enhance the signal of particles corresponding to copies of the same type of macromolecular allow obtaining much higher resolution insights into macromolecules. Here, I review the developments in subtomogram analysis at Wolfgang Baumeister's laboratory that make the dream of structural biology in the native cell become reality.

Original language	English
Article number	100063
Journal	Journal of Structural Biology: X
Volume	6
DOIs	https://doi.org/10.1016/j.yjsbx.2022.100063
Publication status	Published - Feb 2022

Bibliographical note

Funding Information:
Friedrich Förster reports financial support was provided by European Research Council. Friedrich Förster reports financial support was provided by Nederlandse Organisatie voor Wetenschappelijk Onderzoek Utrecht.

Funding Information:
I would like to thank Wolfgang Baumeister for inspiration and mentorship throughout my scientific career. I am grateful to Max Gemmer for contributing Fig. 3 and to Stuart Howes for carefully reading the manuscript. I received support from the European Research Council (ERC-Consolidator grant 724425 , Biogenesis and Degradation of Endoplasmic Reticulum Proteins) and the Dutch Research Council NWO (Vici 724.016.001 and TA 741.018.201).

Publisher Copyright:
© 2022

Funding

Friedrich Förster reports financial support was provided by European Research Council. Friedrich Förster reports financial support was provided by Nederlandse Organisatie voor Wetenschappelijk Onderzoek Utrecht. I would like to thank Wolfgang Baumeister for inspiration and mentorship throughout my scientific career. I am grateful to Max Gemmer for contributing Fig. 3 and to Stuart Howes for carefully reading the manuscript. I received support from the European Research Council (ERC-Consolidator grant 724425 , Biogenesis and Degradation of Endoplasmic Reticulum Proteins) and the Dutch Research Council NWO (Vici 724.016.001 and TA 741.018.201).

Keywords

Correlation
Cryo-electron tomography
Image analysis
Native structural biology
Subtomogram averaging

Access to Document

10.1016/j.yjsbx.2022.100063Licence: CC BY

1-s2.0-S2590152422000046-mainFinal published version, 2.94 MBLicence: CC BY

Cite this

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title = "Subtomogram analysis: The sum of a tomogram's particles reveals molecular structure in situ",

abstract = "Cryo-electron tomography is uniquely suited to provide insights into the molecular architecture of cells and tissue in the native state. While frozen hydrated specimens tolerate sufficient electron doses to distinguish different types of particles in a tomogram, the accumulating beam damage does not allow resolving their detailed molecular structure individually. Statistical methods for subtomogram averaging and classification that coherently enhance the signal of particles corresponding to copies of the same type of macromolecular allow obtaining much higher resolution insights into macromolecules. Here, I review the developments in subtomogram analysis at Wolfgang Baumeister's laboratory that make the dream of structural biology in the native cell become reality.",

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N2 - Cryo-electron tomography is uniquely suited to provide insights into the molecular architecture of cells and tissue in the native state. While frozen hydrated specimens tolerate sufficient electron doses to distinguish different types of particles in a tomogram, the accumulating beam damage does not allow resolving their detailed molecular structure individually. Statistical methods for subtomogram averaging and classification that coherently enhance the signal of particles corresponding to copies of the same type of macromolecular allow obtaining much higher resolution insights into macromolecules. Here, I review the developments in subtomogram analysis at Wolfgang Baumeister's laboratory that make the dream of structural biology in the native cell become reality.

AB - Cryo-electron tomography is uniquely suited to provide insights into the molecular architecture of cells and tissue in the native state. While frozen hydrated specimens tolerate sufficient electron doses to distinguish different types of particles in a tomogram, the accumulating beam damage does not allow resolving their detailed molecular structure individually. Statistical methods for subtomogram averaging and classification that coherently enhance the signal of particles corresponding to copies of the same type of macromolecular allow obtaining much higher resolution insights into macromolecules. Here, I review the developments in subtomogram analysis at Wolfgang Baumeister's laboratory that make the dream of structural biology in the native cell become reality.

KW - Correlation

KW - Cryo-electron tomography

KW - Image analysis

KW - Native structural biology

KW - Subtomogram averaging

UR - https://www.scopus.com/pages/publications/85123978701

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DO - 10.1016/j.yjsbx.2022.100063

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VL - 6

JO - Journal of Structural Biology: X

JF - Journal of Structural Biology: X

M1 - 100063

ER -

Subtomogram analysis: The sum of a tomogram's particles reveals molecular structure in situ

Abstract

Bibliographical note

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Keywords

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