From cells to atoms: Cryo-EM as an essential tool to investigate pathogen biology, host-pathogen interaction, and drug discovery.

Autor: Shepherd DC; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia., Dalvi S; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia., Ghosal D; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia.
Jazyk: angličtina
Zdroj: Molecular microbiology [Mol Microbiol] 2022 Mar; Vol. 117 (3), pp. 610-617. Date of Electronic Publication: 2021 Oct 23.
DOI: 10.1111/mmi.14820
Abstrakt: Electron cryo-microscopy (cryo-EM) has lately emerged as a powerful method in structural biology and cell biology. While cryo-EM single-particle analysis (SPA) is now routinely delivering structures of purified proteins and protein complexes at near-atomic resolution, the use of electron cryo-tomography (cryo-ET), together with subtomogram averaging, is allowing visualization of macromolecular complexes in their native cellular environment, at unprecedented resolution. The unique ability of cryo-EM to provide information at many spatial resolution scales from ångströms to microns makes it an invaluable tool that bridges the classic "resolution-gap" between structural biology and cell biology domains. Like in many other fields of biology, in recent years, cryo-EM has revolutionized our understanding of pathogen biology, host-pathogen interaction and has made significant strides toward structure-based drug discovery. In a very recent example, during the ongoing coronavirus disease (COVID-19) pandemic, the structure of the stabilized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein was deciphered by SPA. This led to the development of multiple vaccines. Alongside, cryo-ET provided key insights into the structure of the native virion, mechanism of its entry, replication, and budding; demonstrating the unrivaled power of cryo-EM in investigating pathogen biology, host-pathogen interaction, and drug discovery. In this review, we showcase a few examples of how different imaging modalities within cryo-EM have enabled the study of microbiology and host-pathogen interaction.
(© 2021 John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: