Dynamics of Membrane Proteins using High-Speed Atomic Force Microscopy

Session

Poster Session Two

Authors

Abeer Alshammari (3, 4), Robin Bon (2), Edmund Kunji (1), George Heath (3)

Affiliations

1. Medical Research Council Mitochondrial Biology Unit, University of Cambridge
2. School of Medicine, University of Leeds
3. School of Physics and Astronomy, University of Leeds
4. Department of Physics, College of Science, University of Hafr Al Batin

Keywords

AFM, membrane protein, dynamics

Abstract text

Membrane proteins such as ion channels and transporters are involved in a variety of biological processes such as sensing, signal transmission, and molecule distribution regulation. The dysfunctions of these membrane proteins have been implicated in many diseases, and they might be a great therapeutic target for a variety of diseases. In order to gain deeper insights into the mechanism of action of these proteins, it is important to require knowledge of protein structures and dynamics. High-Speed Atomic Force Microscopy (HS-AFM) allows us to monitor individual proteins in action under physiological environments with high spatiotemporal resolution of around 1 nm and 100 ms [1]. Here, we start to use HS-AFM to study the structural dynamics of Transient receptor potential canonical 5 (TRPC5) ion channels, to understand how these ion channels open and respond to small molecules. TRPC structures reported so far represent static pictures of closed channel states in non-native environments [2]. Also, we investigated the effect of curvature on membrane proteins conformation. In another project we aim to quantify the interaction strength between mitochondrial ATP/ADP carriers to determine whether they exist and operate as monomers or dimers, because of conflicting reports in the literature [3].

References

[1] G. R. Heath and S. Scheuring, “Advances in high-speed atomic force microscopy (HS-AFM) reveal dynamics of transmembrane channels and transporters,” Current Opinion in Structural Biology, vol. 57. Elsevier Ltd, pp. 93–102, 2019, doi: 10.1016/j.sbi.2019.02.008.

[2] A. Minard et al., “Remarkable progress with small-molecule modulation of TRPC1/4/5 channels: implications for understanding the channels in health and disease,” Cells, vol. 7, no. 6, p. 52, 2018.

[3] E. R. S. Kunji and J. J. Ruprecht, “The mitochondrial ADP/ATP carrier exists and functions as a monomer,” Biochem. Soc. Trans., vol. 48, no. 4, pp. 1419–1432, Aug. 2020, doi: 10.1042/BST20190933.