Atom Probe Tomography for 3D Structural and Chemical Analysis of Individual Proteins
Journal article, 2019

Determination of the 3D structure of proteins and other biomolecules is a major goal in structural biology, to provide insights to their biological function. Such structures are historically unveiled experimentally by X-ray crystallography or NMR spectroscopy, and in recent years using cryo-electron microscopy. Here, a method for structural analysis of individual proteins on the sub-nanometer scale using atom probe tomography is described. This technique offers a combination of high-resolution analysis of biomolecules in 3D, and the chemical sensitivity of mass spectrometry. As a model protein, the well-characterized antibody IgG is used. IgG is encapsulated in an amorphous solid silica matrix via a sol–gel process to provide the requisite support for atom probe analysis. The silica synthesis is tuned to resemble physiological conditions. The 3D reconstructions show good agreement with the protein databank IgG crystal structure. This suggests that the silica-embedding strategy can open the field of atom probe tomography to the analysis of biological molecules. In addition to high-resolution structural information, the technique may potentially provide chemical information on the atomic scale using isotopic labeling. It is envisaged that this method may constitute a useful complement to existing tools in structural biology, particularly for the examination of proteins with low propensity for crystallization.

atom probe tomography

sol–gel

mass spectrometry

structural biology

immunoglobulin G

Author

Gustav Sundell

Chalmers, Chemistry and Chemical Engineering, Applied Chemistry, Martin Andersson Group

Mats Hulander

Chalmers, Chemistry and Chemical Engineering, Applied Chemistry

Astrid Pihl

Chalmers, Chemistry and Chemical Engineering, Applied Chemistry, Martin Andersson Group

Martin Andersson

Chalmers, Chemistry and Chemical Engineering, Applied Chemistry, Martin Andersson Group

Small

1613-6810 (ISSN) 1613-6829 (eISSN)

Vol. in press 1900316

Subject Categories

Biochemistry and Molecular Biology

Biophysics

Structural Biology

DOI

10.1002/smll.201900316

More information

Latest update

5/20/2019