Table 2.

Summary of PD-related point mutations of α-syn and their effects on its binding to membranes.

PTM	Position	Effects on Membranes	Ref.
Phosphorylation	Y39	diminished lipid binding of α-syn and increased axonal pathology in transgenic PD mice	[152]
	S87	conformational change in membrane-bound α-syn decreased affinity to lipid vesicles reduced aggregation of α-syn	[153]
	S129	reduced binding of α-syn monomers and Fe3+-induced oligomers to lipid vesicles fewer α-helical structures, decreased binding, and disruption of lipid vesicles no difference in membrane binding to synaptosomes in the A30P variant, α-syn membrane binding was increased, leading to disruption of membranes in the A53T variant, binding to membranes was reduced	[154,155,156]
Acetylation	M1	increased affinity of α-syn to membrane binding without structural alterations	[157]
Nitration	Y39	less α-helical structure formation upon lipid vesicle binding disrupted binding affinity of α-syn to membranes	[158]
	Y125	less α-helical structure formation upon lipid vesicle binding disrupted binding affinity of α-syn to membranes
	Y133, Y136	disrupted binding affinity of α-syn to lipid vesicles
Ubiquitination	K6, K23, K43, K96	no alterations in secondary structure of α-syn upon lipid binding	[159,160]
Truncation	1–100	less potential inducing curvature upon membrane binding compared to full-length protein	[161]
	1–103	produces mature fibrils in the presence of phospholipid vesicles	[162]
	1–115	upon lipid binding, 1–115 truncated α-syn shows higher α-helical levels compared to full-length α-syn facilitating lipid binding	[163]
	1–119	aggregates faster than full-length α-syn in the presence of phospholipid vesicles	[162]
	1–120	reduced α-syn fibrillation and increased lipid binding predisposition upon methylphenidate treatment	[164]
	1–121	similar aggregation to full-length α-syn in the presence of phospholipid vesicles decreased ability to distort phospholipid membranes higher toxicity compared to full-length α-syn	[165]
Glycosylation	T72	reduction in fibril formation, aggregation, and toxicity of monomeric α-syn in vitro, while binding affinity to lipid vesicles was unaltered	[166]
	T75	reduction in fibril formation, aggregation, and toxicity of monomeric α-syn in vitro, while binding affinity to lipid vesicles was unaltered
	T81	reduction in fibril formation, aggregation, and toxicity of monomeric α-syn in vitro, while binding affinity to lipid vesicles was unaltered
	S87	reduction in fibril formation, aggregation, and toxicity of monomeric α-syn in vitro, while binding affinity to lipid vesicles was unaltered
	T72, T75, and T81	inhibited the α-helical structure of α-syn upon membrane binding
Glycation	Lysine	reduced binding affinity towards sodium dodecyl sulfate (SDS) micelles without affecting the α-helical structure of α-syn disruption of lipid vesicles upon α-syn binding	[167]