Disordered-to-ordered structural changes of SNAP-25 are modulated by environmental conditions

SNARE-mediated vesicle-membrane fusion is an essential process in neuronal exocytosis in which SNARE proteins drive fusion by winding together to form a 4-helix coiled-coil. In doing this, SNAREs undergo a dramatic disorder-to-order transition that provides energy for vesicle-membrane fusion. Understanding the structural dynamics of these proteins is critical to understanding the mechanisms of this process. SNAP-25 contributes two α-helices, SN1 and SN2, to the SNARE complex. Using NMR and Circular Dichroism (CD) Spectroscopy, we show that SNAP-25 is best described as an intrinsically disordered protein that folds into more ordered domains in response to changes in environmental conditions (pH, ionic strength, and temperature).