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

By Daniel A. Holdbrook, Yuk Ming Leung, T Piggot, Phedra Marius, Phillip T.F. Williamson and Syma Khalid


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

Topics: QC, QD
Year: 2010
OAI identifier:
Provided by: e-Prints Soton

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  10. (2000). Comparative protein structure modeling of genes and genomes, doi
  11. (2004). DICHROWEB, an online server for protein secondary structure analyses from circular dichroism spectroscopic data, doi
  12. (1984). Differential light scattering and absorption flattening optical effects are minimal in the circular dichroism spectra of small unilamellar vesicles, doi
  13. (1981). Estimation of globular protein secondary structure from circular dichroism, doi
  14. (1990). Estimation of protein secondary structure and error analysis from circular dichroism spectra, doi
  15. (2010). Expression and purification of the transmembrane domain of Fukutin-I for biophysical studies, doi
  16. (2007). Fukutin-related protein localizes to the Golgi apparatus and mutations lead to mislocalization in muscle in vivo, doi
  17. (2005). Fukutin-related protein mutations that cause congenital muscular dystrophy result in ER-retention of the mutant protein in cultured cells, doi
  18. (1995). Gromacs - a Message-Passing Parallel Molecular-Dynamics Implementation, doi
  19. (2008). GROMACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation, doi
  20. (2005). Gromacs: Fast, Flexible, and Free, doi
  21. (2006). Insertion and assembly of membrane proteins via simulation, doi
  22. (1998). Lipids of the Golgi membrane, doi
  23. (1998). Localization of proteins to the Golgi apparatus, doi
  24. (1993). Main-chain bond lengths and bond angles in protein structures, doi
  25. (2009). Martini Coarse-Grained Force Field: Extension to Carbohydrates, doi
  26. (1997). Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature, doi
  27. (1984). Molecular-Dynamics with Coupling to an External Bath, doi
  28. (2008). P-LINCS: A parallel linear constraint solver for molecular simulation, doi
  29. (2008). POMT2, a key enzyme in Walker-Warburg syndrome: somatic sPOMT2, but not testis specific POMT2, is crucial for mannosyltransferase activity in vivo., doi
  30. (2003). Protein glycosylation in disease: new insights into the congenital muscular dystrophies, doi
  31. (2008). Protein secondary structure analyses from circular dichroism spectroscopy: methods and reference databases, doi
  32. (2008). Self-assembly of a simple membrane protein: Coarse-grained molecular dynamics simulations of the influenza M2 channel, doi
  33. (1992). Settle - an Analytical Version of the Shake and Rattle Algorithm for Rigid Water Models, doi
  34. (1993). Sorting of membrane proteins in the secretory pathway, doi
  35. (2005). Sub-cellular localisation of fukutin related protein in different cell lines and in the muscle patients with MDC1C and LGMD2I, doi
  36. (2004). Subcellular localization of fukutin and fukutin-related protein in muscle cells, doi
  37. (1998). Targeting of proteins to the Golgi apparatus, doi
  38. (2007). The MARTINI force field: coarse grained model for biomolecular simulations, doi
  39. (2001). Trafficking and localisation of resident Golgi glycosylation enzymes, doi
  40. (1997). Transmembrane domain-dependent sorting of proteins to the ER and plasma membrane in yeast, doi
  41. (1996). VMD: Visual molecular dynamics, doi

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