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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388955%3A_____%2F17%3A00478166" target="_blank" >RIV/61388955:_____/17:00478166 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.7554/eLife.28985.001" target="_blank" >http://dx.doi.org/10.7554/eLife.28985.001</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.7554/eLife.28985.001" target="_blank" >10.7554/eLife.28985.001</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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)P2-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)P2 and heparan sulfates on opposing sides of the membrane. Based on atomistic molecular dynamics simulations, we propose a mechanism that drives PI(4,5)P2 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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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)P2-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)P2 and heparan sulfates on opposing sides of the membrane. Based on atomistic molecular dynamics simulations, we propose a mechanism that drives PI(4,5)P2 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

<a href="/cs/project/GC14-03141J" target="_blank" >GC14-03141J: Studium vztahu struktury a funkce FGF2 oligomerů tvořících membránové póry technikami zaměřenými na sledování jedné molekuly</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

eLife

ISSN

2050-084X

e-ISSN

—

Svazek periodika

6

Číslo periodika v rámci svazku

2017

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

36

Strana od-do

—

Kód UT WoS článku

000410744600001

EID výsledku v databázi Scopus

2-s2.0-85029789831