Exploring the structure function relationship of membrane-pore-forming Fibroblast Growth Factor 2 (FGF2) oligomers with single molecule fluorescence microscopy

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Exploring the structure-function relationship of membrane-pore-forming Fibroblast Growth Factor 2 (FGF2) oligomers is crucial for understanding its unique mechanism of non-classical secretion, a process vital for tissue repair and angiogenesis. FGF2 forms oligomeric pores in the plasma membrane, facilitating its release without the involvement of the classical secretion pathway. Despite its importance, the molecular details of how FGF2 oligomers assemble, interact with membranes, and regulate pore formation remain largely unclear. By using single-molecule fluorescence microscopy, we can observe these dynamic processes in real-time, providing unprecedented insights into the structural arrangements and functional mechanisms of FGF2 at the single-molecule level. 

 

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You can read more on this topic in the following recent publications:

  • Lolicato F, Steringer JP, Saleppico R, Beyer D, Fernandez-Sobaberas J, Unger S, Klein S, Riegerová P, Wegehingel S, Müller HM, Schmitt XJ, Kaptan S, Freund C, Hof, M, Šachl R, Chlanda P, Vattulainen I, and Nickel W Disulfide bridge-dependent dimerization triggers FGF2 membrane translocation into the extracellular space eLife 2024
  • Singh, V.; Riegerová, P.; Steringer, J. P.; Müller, H.-M.; Lolicato, F.; Nickel, W.; Hof, M.; Šachl, R. Determining the Functional Oligomeric State of Membrane- Associated Protein Oligomers Forming Membrane Pores on Giant Lipid Vesicles. Anal. Chem. 2023, 95, 8807–8815.
  • Šachl, R.; Čujová, S.; Singh, V.; Riegerová, P.; Kapusta, P.; Müller, H.-M.; Steringer, J. P.; Hof, M.; Nickel, W. Functional Assay to Correlate Protein Oligomerization States with Membrane Pore Formation. Anal. Chem. 2020, 92, 14861–14866.

Steringer, J. P., Lange, S., Čujová, S., Šachl, R., Poojari, C., Lolicato, F., … Nickel, W. Key steps in unconventional secretion of fibroblast growth factor 2 reconstituted with purified components. eLife, 6 (2017).