Key steps in unconventional secretion of fibroblast growth factor 2 reconstituted with purified components

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http://hdl.handle.net/10138/225121

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Steringer , J P , Lange , S , Cujova , S , Sachi , R , Poojari , C , Lolicato , F , Beutel , O , Mueller , H-M , Unger , S , Coskun , U , Honigmann , A , Vattulainen , I , Hof , M , Freund , C & Nickel , W 2017 , ' Key steps in unconventional secretion of fibroblast growth factor 2 reconstituted with purified components ' , eLife , vol. 6 , 28985 . https://doi.org/10.7554/eLife.28985

Title: Key steps in unconventional secretion of fibroblast growth factor 2 reconstituted with purified components
Author: Steringer, Julia P.; Lange, Sascha; Cujova, Sabina; Sachi, Radek; Poojari, Chetan; Lolicato, Fabio; Beutel, Oliver; Mueller, Hans-Michael; Unger, Sebastian; Coskun, Uenal; Honigmann, Alf; Vattulainen, Ilpo; Hof, Martin; Freund, Christian; Nickel, Walter
Contributor: University of Helsinki, Department of Physics
University of Helsinki, Department of Physics
University of Helsinki, Department of Physics
Date: 2017-07-19
Language: eng
Number of pages: 36
Belongs to series: eLife
ISSN: 2050-084X
URI: http://hdl.handle.net/10138/225121
Abstract: FGF2 is secreted from cells by an unconventional secretory pathway. This process is mediated by direct translocation across the plasma membrane. Here, we define the minimal molecular machinery required for FGF2 membrane translocation in a fully reconstituted inside-out vesicle system. FGF2 membrane translocation is thermodynamically driven by PI(4,5)P-2-induced membrane insertion of FGF2 oligomers. The latter serve as dynamic translocation intermediates of FGF2 with a subunit number in the range of 8-12 FGF2 molecules. Vectorial translocation of FGF2 across the membrane is governed by sequential and mutually exclusive interactions with PI(4,5)P-2 and heparan sulfates on opposing sides of the membrane. Based on atomistic molecular dynamics simulations, we propose a mechanism that drives PI(4,5)P-2 dependent oligomerization of FGF2. Our combined findings establish a novel type of self-sustained protein translocation across membranes revealing the molecular basis of the unconventional secretory pathway of FGF2.
Subject: MOLECULAR-DYNAMICS METHOD
ADDITIVE FORCE-FIELD
PARTICLE MESH EWALD
PROTEIN SECRETION
MAMMALIAN-CELLS
PLASMA-MEMBRANE
HIV-1 TAT
NMR-SPECTROSCOPY
EXPORT MACHINERY
SIMULATIONS
1182 Biochemistry, cell and molecular biology
114 Physical sciences
116 Chemical sciences
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