The University of Southampton
University of Southampton Institutional Repository

Stability and membrane orientation of the fukutin transmembrane domain: a combined multiscale molecular dynamics and circular dichroism study

Holdbrook, Daniel A., Leung, Yuk Ming, Piggot, T, Marius, Phedra, Williamson, Phillip T.F. and Khalid, Syma (2010) Stability and membrane orientation of the fukutin transmembrane domain: a combined multiscale molecular dynamics and circular dichroism study Biochemistry, 49, (51), pp. 10796-10802. (doi:10.1021/bi101743w). (PMID:21105749).

Record type: Article


The N-terminal domain of Fukutin-I has been implicated in the localization of the protein in the endoplasmic reticulum/Golgi apparatus. It has been proposed to mediate this through its interaction with the thinner lipid bilayers found in these compartments. Here we have employed multi-scale molecular dynamics simulations and circular dichroism spectroscopy to explore the structure, stability and orientation of the short 36-residue N-terminal of Fukutin-I (FK1TMD) in lipids of differing tail lengths. Our results show that FK1TMD adopts a stable helical conformation in phosphatidylcholine lipids when orientated with its principal axis perpendicular to the bilayer plane. The stability of the helix is largely insensitive to the lipid tail length, avoiding hydrophobic mismatch by virtue of its mobility and ability to tilt within the lipid bilayers. This suggests that changes in FK1TMD tilt in response to bilayer properties may be implicated in the regulation of its trafficking. Coarse-grained simulations of the complex Golgi membrane suggest the N-terminal domain may induce the formation of microdomains in the surrounding membrane through its preferential interaction with 1,2-dipalmitoyl-sn-glycero-3-phoshpatidylinositol 4,5-bisphosphate (PIP2) lipids.

Text Holdbrook2010.pdf - Version of Record
Download (3MB)

More information

Published date: 28 December 2010


Local EPrints ID: 173815
ISSN: 0006-2960
PURE UUID: cf6dbbdc-cb84-4cf2-a1d2-fdf266a4d420
ORCID for Phillip T.F. Williamson: ORCID iD

Catalogue record

Date deposited: 08 Feb 2011 09:25
Last modified: 03 Oct 2017 16:41

Export record



Author: Daniel A. Holdbrook
Author: Yuk Ming Leung
Author: T Piggot
Author: Phedra Marius
Author: Syma Khalid

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton:

ePrints Soton supports OAI 2.0 with a base URL of

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.