Cooperation of helix insertion and lateral pressure to remodel membranes

April 9, 2019

Title

Cooperation of helix insertion and lateral pressure to remodel membranes

Author

Mohammad A.A. Fakhree, Sjoerd A. J. Engelbertink, Kirsten A. van Leijenhorst-Groener, Christian Blum, Mireille M. A. E. Claessens

Year

2019

Journal

Biomacromolecules

Abstract

Nature has developed different protein mediated mechanisms to remodel cellular membranes. One of the proteins that is implicated in these processes is α-synuclein (αS). Here we investigate if besides αS’s membrane bound amphipathic helix the disordered, solvent exposed tail of the protein contributes to membrane reshaping. We produced αS variants with elongated or truncated disordered solvent exposed domains. We observe a transformation of opaque multi lamellar vesicle solutions into non-scattering solutions containing smaller structures upon addition of all αS variants. Experimental data combined with model calculations show that the cooperation of helix insertion and lateral pressure exerted by the disordered domain makes the full length protein decidedly more efficient in membrane remodeling than the truncated version. Using disordered domains may not only be cost efficient, it may also add a new level of control over vesicle fusion/fission by expansion or compaction of the domain.

Instrument

J-1500

Keywords

Circular dichroism, Secondary structure, Membrane interactions, Chemical stability, Biochemistry