Hybrids of SNARE Transmembrane Domains and Artificial Recognition Motifs as Membrane Fusion Inducing Model Peptides

Hybrids of SNARE Transmembrane Domains and Artificial Recognition Motifs as Membrane Fusion Inducing Model Peptides

Jan-Dirk Wehland

Doctoral thesis

Date of Examination: 2017-12-08

Date of issue: 2018-03-13

Advisor: Diederichsen, Ulf Prof. Dr.

Referee: Diederichsen, Ulf Prof. Dr.

Referee: Jahn, Reinhard Prof. Dr.

Referee: Tittmann, Kai Prof. Dr.

Referee: Feussner, Ivo Prof. Dr.

Referee: Das, Shoubhik Dr.

Referee: Thomas, Franziska Dr.

Persistent Address: http://hdl.handle.net/11858/00-1735-0000-002E-E384-1

Files in this item

Name: Doctoral thesis_Jan-Dirk Wehland.pdf

Size: 6,0 MB

Format: PDF

View/Open

The following license files are associated with this item:

Creative Commons

Abstract

English

Protein mediated fusion of membranes is a crucial biological process. For instance, SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor) proteins are involved in neuronal exocytosis. However, the knowledge about mechanistic details is still incomplete. The herein presented peptide hybrids based on the native linker and transmembrane domains of the SNARE key actors synaptobrevin 2 (Syb) and syntaxin 1A (Sx) as well as artificial recognition units based on peptide nuleic acids (PNA) or coiled-coil forming peptides (E3/K3) constitute a well controllable tool for the investigation of SNARE mediated membrane fusion. The focus is on C-terminally modified transmembrane domains which were mainly tested in FRET (Förster resonance energy transfer) related bulk leaflet mixing experiments. It was revealed that increased C-terminal negative charges hamper the fusion efficiency, whereas the removal of charges amplifies membrane fusion.

Keywords: Membrane fusion; SNARE mimetics; C-terminal charge of SNARE transmembrane domains; FRET based bulk leaflet mixing assays