Direct NMR evidence for transient binding of the vesicular SNARE protein synaptobrevin-2/VAMP2 to the α-synuclein C-terminus

NMR, MST, and BLI show that the α-synuclein C-terminus binds transiently to synaptobrevin-2/VAMP2 with a Kd in the 10–50 micromolar range.

• Why it matters: The physiological role of α-synuclein is unclear, and linking it to neuronal exocytosis requires direct evidence for how it engages exocytic proteins.
• What they did: Using NMR chemical shift perturbation and paramagnetic relaxation enhancement, the study mapped binding to α-synuclein residues V118–E137 and to the synaptobrevin-2 SNARE motif/linker interface (A82–K87), with effects on synaptobrevin-2 N-terminus (M1–S2).
• The result: The NMR CSP and PRE signals indicate fast-exchange transient binding (s–ms), supporting a regulatory, multi-partner interaction model upstream of or during neuronal exocytosis.

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