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

Stability and membrane orientation of the fukutin transmembrane domain: a combined multiscale molecular dynamics and circular dichroism study
Stability and membrane orientation of the fukutin transmembrane domain: a combined multiscale molecular dynamics and circular dichroism study
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.
0006-2960
10796-10802
Holdbrook, Daniel A.
d114c018-fb42-4a49-9b50-f7739feb75f5
Leung, Yuk Ming
20384feb-566e-4022-946e-2540053fb000
Piggot, T
75829b71-d73b-43d1-b24f-3e70c2c4d0c8
Marius, Phedra
f5bf8a27-2332-4d04-a45b-4b2677fcc865
Williamson, Phillip T.F.
0b7715c6-b60e-4e95-a1b1-6afc8b9f372a
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Holdbrook, Daniel A.
d114c018-fb42-4a49-9b50-f7739feb75f5
Leung, Yuk Ming
20384feb-566e-4022-946e-2540053fb000
Piggot, T
75829b71-d73b-43d1-b24f-3e70c2c4d0c8
Marius, Phedra
f5bf8a27-2332-4d04-a45b-4b2677fcc865
Williamson, Phillip T.F.
0b7715c6-b60e-4e95-a1b1-6afc8b9f372a
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394

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), 10796-10802. (doi:10.1021/bi101743w). (PMID:21105749)

Record type: Article

Abstract

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.

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Published date: 28 December 2010

Identifiers

Local EPrints ID: 173815
URI: http://eprints.soton.ac.uk/id/eprint/173815
ISSN: 0006-2960
PURE UUID: cf6dbbdc-cb84-4cf2-a1d2-fdf266a4d420
ORCID for Phillip T.F. Williamson: ORCID iD orcid.org/0000-0002-0231-8640
ORCID for Syma Khalid: ORCID iD orcid.org/0000-0002-3694-5044

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Date deposited: 08 Feb 2011 09:25
Last modified: 20 Jul 2019 00:53

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