Membrane Binding Induces Distinct Structural Signatures in the Mouse Complexin-1C-Terminal Domain

Area of Science:

• Biochemistry
• Molecular Biology
• Neuroscience

Background:

• Complexins are key regulators of SNARE-mediated exocytosis in synaptic vesicles.
• Evolutionary variations in complexin function impact the inhibition of spontaneous vesicle fusion.

Purpose of the Study:

• To characterize the structure and dynamics of the mouse complexin-1 C-terminal domain (mCpx1 CTD).
• To investigate the mCpx1 CTD's interaction with membranes and membrane mimetics.
• To identify structural basis for evolutionary differences in complexin function.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy
• Electron Spin Resonance (ESR) spectroscopy
• Optical spectroscopies

Main Results:

• The mCpx1 CTD is disordered in the absence of lipids, with a short N-terminal helix.
• In the presence of micelles and small unilamellar vesicles, the mCpx1 CTD forms a discontinuous helical structure.
• Distinct lipid compositional preferences were observed for mCpx1 CTD interactions with large unilamellar vesicles.

Conclusions:

• Structural differences in the mCpx1 CTD compared to worm complexin (wCpx1 CTD) were identified in critical regions.
• These structural divergences suggest a potential mechanism for evolutionary variations in complexin-mediated inhibition of spontaneous synaptic vesicle fusion.