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), 10796-10802. (doi:10.1021/bi101743w). (PMID:21105749).
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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.
|Subjects:||Q Science > QC Physics
Q Science > QD Chemistry
|Divisions:||University Structure - Pre August 2011 > School of Biological Sciences
University Structure - Pre August 2011 > School of Chemistry
|Date Deposited:||08 Feb 2011 09:25|
|Last Modified:||14 Apr 2014 10:54|
OMSys: Towards a systems model of a bacterial outer membrane
Funded by: BBSRC (BB/H000658/1)
Led by: Syma Khalid
1 December 2009 to 30 November 2012
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