دورية أكاديمية
أعرض في EDS

Intrinsic Disorder of the Neuronal SNARE Protein SNAP25a in its Pre-fusion Conformation.

التفاصيل البيبلوغرافية
العنوان: Intrinsic Disorder of the Neuronal SNARE Protein SNAP25a in its Pre-fusion Conformation.
المؤلفون: Stief T; Forschungszentrum Jülich, Structural Biochemistry (IBI-7) and Jülich Center for Structural Biology (JuStruct), Wilhelm-Johnen-Straße, 52425 Jülich, Germany; Heinrich Heine University of Düsseldorf, Physical Biology, Universitätsstraße 1, 40225 Düsseldorf, Germany., Gremer L; Forschungszentrum Jülich, Structural Biochemistry (IBI-7) and Jülich Center for Structural Biology (JuStruct), Wilhelm-Johnen-Straße, 52425 Jülich, Germany; Heinrich Heine University of Düsseldorf, Physical Biology, Universitätsstraße 1, 40225 Düsseldorf, Germany., Pribicevic S; Max-Planck Institute for Multidisciplinary Sciences, Dept. of Neurobiology, Am Faßberg 11, 37077 Göttingen, Germany., Espinueva DF; Max-Planck Institute for Multidisciplinary Sciences, Dept. of Neurobiology, Am Faßberg 11, 37077 Göttingen, Germany., Vormann K; Forschungszentrum Jülich, Structural Biochemistry (IBI-7) and Jülich Center for Structural Biology (JuStruct), Wilhelm-Johnen-Straße, 52425 Jülich, Germany; Heinrich Heine University of Düsseldorf, Physical Biology, Universitätsstraße 1, 40225 Düsseldorf, Germany., Biehl R; Jülich Centre for Neutron Science (JCNS-1) and Institute for Biological Information Processing (IBI-8), Forschungszentrum Jülich GmbH, 52428 Jülich, Germany., Jahn R; Max-Planck Institute for Multidisciplinary Sciences, Dept. of Neurobiology, Am Faßberg 11, 37077 Göttingen, Germany., Pérez-Lara Á; Dept. of Physical Chemistry, University of Granada, Campus Universitario de Cartuja, 18071 Granada, Spain., Lakomek NA; Forschungszentrum Jülich, Structural Biochemistry (IBI-7) and Jülich Center for Structural Biology (JuStruct), Wilhelm-Johnen-Straße, 52425 Jülich, Germany; Heinrich Heine University of Düsseldorf, Physical Biology, Universitätsstraße 1, 40225 Düsseldorf, Germany. Electronic address: Nils-Alexander.Lakomek@hhu.de.
المصدر: Journal of molecular biology [J Mol Biol] 2023 May 15; Vol. 435 (10), pp. 168069. Date of Electronic Publication: 2023 Mar 30.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 2985088R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1089-8638 (Electronic) Linking ISSN: 00222836 NLM ISO Abbreviation: J Mol Biol Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier
Original Publication: 1959- : London : Academic Press
مواضيع طبية MeSH: Membrane Fusion* , Neurons*/metabolism , SNARE Proteins*/metabolism, Protein Conformation ; Scattering, Small Angle ; X-Ray Diffraction ; Humans
مستخلص: 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
فهرسة مساهمة: Keywords: NMR spectroscopy; SNAP25a; SNARE proteins; intrinsically disordered proteins; protein dynamics
المشرفين على المادة: 0 (SNARE Proteins)
0 (SNAP25 protein, human)
تواريخ الأحداث: Date Created: 20230401 Date Completed: 20230525 Latest Revision: 20230622
رمز التحديث: 20230623
DOI: 10.1016/j.jmb.2023.168069
PMID: 37003471
قاعدة البيانات: MEDLINE
الوصف
تدمد:1089-8638
DOI:10.1016/j.jmb.2023.168069