Understanding alpha-Synuclein-Membrane Interactions

Current: Miah Turke
Alumni: Krishna Raghavan, Sofi Maltseva, Ben Slaw, Peter Chung, Luke Hwang, Alessandra Leong

Alpha-synuclein (aSyn) is an intrinsically disordered, neuronal protein implicated in Parkinson’s Disease (PD) and the formation of Lewy Bodies. The normal function of the protein is related to its interaction with synaptic vesicles during the synaptic vesicle cycle. There are several PD-associated mutations to aSyn are known and affect membrane-binding behavior. Our work currently focuses on understanding this protein-membrane interaction in greater detail- what does a binding site mean for aSyn? How are the binding modes different for PD mutants? (Maltseva, et al, 2024) How do WT aSyn binding modes change when membrane conditions change? (Turke, et al, in progress) To answer these questions, we currently use a combination of biophysical techniques including a tryptophan fluorescence binding assay, tethered-vesicle microscopy assay, and fluorescence polarization anisotropy. Previous work on this system in our group made use of spherical nanoparticle supported lipid bilayers (SSLBs) to control the curvature of the membrane and were used in conjunction with small angle x-ray scattering (SAXS) and x-ray photon correlation spectroscopy (XPCS). (Chung, et al, 2019; Chung, et al, 2020)

Selected bibliography

Maltseva, S., Kerr, D., Turke, M., Adams, E. J., & Lee, K. Y. (2024b). Parkinson’s disease-associated mutations in α-synuclein alters its lipid-bound state. Biophysical Journal. https://doi.org/10.1016/j.bpj.2024.05.002
Turke, M. Raghavan, K., Maltseva, S., Adams, E. J., & Lee, K. Y. (in review).
Chung, P. J., Zhang, Q., Hwang, H. L., Leong, A., Maj, P., Szczygiel, R., Dufresne, E. M., Narayanan, S., Adams, E. J., & Lee, K. Y. (2019). Α-synuclein sterically stabilizes spherical nanoparticle-supported lipid bilayers. ACS Applied Bio Materials, 2(4), 1413–1419. https://doi.org/10.1021/acsabm.8b00774
Chung, P. J., Hwang, H. L., Slaw, B. R., Leong, A., Adams, E. J., & Lee, K. Y. (2020). The c terminal domain of α‐synuclein confers steric stabilization on synaptic vesicle‐like surfaces. Advanced Materials Interfaces, 7(14). https://doi.org/10.1002/admi.201902151