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001014224 1001_ $$0P:(DE-Juel1)187436$$aStief, Tobias$$b0
001014224 245__ $$aIntrinsic Disorder of the Neuronal SNARE Protein SNAP25a in its Pre-fusion Conformation
001014224 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2023
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001014224 520__ $$aThe neuronal SNARE protein SNAP25a (isoform 2) forms part of the SNARE complex eliciting synaptic vesicle fusion during neuronal exocytosis. While the post-fusion cis-SNARE complex has been studied extensively, little is known about the pre-fusion conformation of SNAP25a. Here we analyze monomeric SNAP25a by NMR spectroscopy, further supported by small-angle X-ray scattering (SAXS) experiments. SAXS data indicate that monomeric SNAP25 is more compact than a Gaussian chain but still a random coil. NMR shows that for monomeric SNAP25a, before SNAP25a interacts with its SNARE partners to drive membrane fusion, only the N-terminal part (region A5 to V36) of the first SNARE motif, SN1 (L11 - L81), is helical, comprising two α-helices (ranging from A5 to Q20 and S25 toV36). From E37 onwards, SNAP25a is mostly disordered and displays high internal flexibility, including the C-terminal part of SN1, almost the entire second SNARE motif (SN2, N144-A199), and the connecting loop region. Apart from the N-terminal helices, only the C-termini of both SN1 (E73 - K79) and SN2 (region T190 - A199), as well as two short regions in the connecting loop (D99 - K102 and E123 - M127) show a weak α-helical propensity (α-helical population < 25%). We speculate that the N-terminal helices (A5 to Q20 and S25 to V36) which constitute the N-terminus of SN1 act as a nucleation site for initiating SNARE zippering.
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001014224 7001_ $$0P:(DE-Juel1)145165$$aGremer, Lothar$$b1
001014224 7001_ $$0P:(DE-HGF)0$$aPribicevic, Sonja$$b2
001014224 7001_ $$0P:(DE-HGF)0$$aEspinueva, Delane F.$$b3
001014224 7001_ $$0P:(DE-Juel1)191152$$aVormann, Katharina$$b4
001014224 7001_ $$0P:(DE-Juel1)130542$$aBiehl, Ralf$$b5
001014224 7001_ $$0P:(DE-HGF)0$$aJahn, Reinhard$$b6
001014224 7001_ $$0P:(DE-HGF)0$$aPérez-Lara, Ángel$$b7
001014224 7001_ $$0P:(DE-Juel1)180657$$aLakomek, Nils$$b8$$eCorresponding author$$ufzj
001014224 773__ $$0PERI:(DE-600)1355192-9$$a10.1016/j.jmb.2023.168069$$gVol. 435, no. 10, p. 168069 -$$n10$$p168069 -$$tJournal of molecular biology$$v435$$x0022-2836$$y2023
001014224 8564_ $$uhttps://juser.fz-juelich.de/record/1014224/files/Stief_et_al_JMB_2023-1.pdf
001014224 8564_ $$uhttps://juser.fz-juelich.de/record/1014224/files/intrinsic-disorder-of-the-neuronal-snare-protein-snap25a-in-its-pre-fusion-conformation.pdf$$yOpenAccess
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