Madej, M. Gregor and Ziegler, Christine M. (2018) Dawning of a new era in TRP channel structural biology by cryo-electron microscopy. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 470 (2). pp. 213-225. ISSN 0031-6768, 1432-2013
Full text not available from this repository. (Request a copy)Abstract
Cryo-electron microscopy (cryo-EM) permits the determination of atomic protein structures by averaging large numbers of individual projection images recorded at cryogenic temperatures-a method termed single-particle analysis. The cryo-preservation traps proteins within a thin glass-like ice layer, making literally a freeze image of proteins in solution. Projections of randomly adopted orientations are merged to reconstruct a 3D density map. While atomic resolution for highly symmetric viruses was achieved already in 2009, the development of new sensitive and fast electron detectors has enabled cryo-EM for smaller and asymmetrical proteins including fragile membrane proteins. As one of the most important structural biology methods at present, cryo-EM was awarded in October 2017 with the Nobel Prize in Chemistry. The molecular understanding of Transient-Receptor-Potential (TRP) channels has been boosted tremendously by cryo-EM single-particle analysis. Several near-atomic and atomic structures gave important mechanistic insights, e.g., into ion permeation and selectivity, gating, as well as into the activation of this enigmatic and medically important membrane protein family by various chemical and physical stimuli. Lastly, these structures have set the starting point for the rational design of TRP channel-targeted therapeutics to counteract life-threatening channelopathies. Here, we attempt a brief introduction to the method, review the latest advances in cryo-EM structure determination of TRP channels, and discuss molecular insights into the channel function based on the wealth of TRP channel cryo-EM structures.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PARTICLE CRYO-EM; ELECTRON CRYOMICROSCOPY STRUCTURE; RESOLUTION; NANODISCS; MODEL; BIOCHEMISTRY; MECHANISMS; INSIGHTS; LIPIDS; PAIN; Membrane transport; TRP channels; Calcium signaling; Single particle cryo-EM; Structure; Lipid-interactions |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Christine Ziegler |
| Depositing User: | Petra Gürster |
| Date Deposited: | 25 Jun 2020 09:57 |
| Last Modified: | 25 Jun 2020 09:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15079 |
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