This title appears in the Scientific Report :
2023
Please use the identifier:
http://dx.doi.org/10.34734/FZJ-2023-03208 in citations.
Please use the identifier: http://dx.doi.org/10.1016/j.jmb.2023.168069 in citations.
Intrinsic Disorder of the Neuronal SNARE Protein SNAP25a in its Pre-fusion Conformation
Intrinsic Disorder of the Neuronal SNARE Protein SNAP25a in its Pre-fusion Conformation
The 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 S...
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Personal Name(s): | Stief, Tobias |
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Gremer, Lothar / Pribicevic, Sonja / Espinueva, Delane F. / Vormann, Katharina / Biehl, Ralf / Jahn, Reinhard / Pérez-Lara, Ángel / Lakomek, Nils (Corresponding author) | |
Contributing Institute: |
Strukturbiochemie; IBI-7 Neutronenstreuung; JCNS-1 |
Published in: | Journal of molecular biology, 435 (2023) 10, S. 168069 - |
Imprint: |
Amsterdam [u.a.]
Elsevier
2023
|
DOI: |
10.34734/FZJ-2023-03208 |
DOI: |
10.1016/j.jmb.2023.168069 |
Document Type: |
Journal Article |
Research Program: |
Information Processing in Neuronal Networks Life Sciences – Building Blocks of Life: Structure and Function Jülich Centre for Neutron Research (JCNS) (FZJ) |
Link: |
Get full text OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://dx.doi.org/10.1016/j.jmb.2023.168069 in citations.
The 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. |