Anchoring of a monotopic membrane protein: the binding of prostaglandin H[sub 2] synthase-1 to the surface of a phospholipid bilayer

Nina, Mafalda; Bernèche, Simon; Roux, Benoît
July 2000
European Biophysics Journal;2000, Vol. 29 Issue 6, p439
Academic Journal
Abstract Prostaglandin H[sub 2] synthases (PGHS-1 and -2) are monotopic peripheral membrane proteins that catalyse the synthesis of prostaglandins in the arachidonate cascade. Picot et al. (1994) proposed that the enzyme is anchored to one leaflet of the bilayer by a membrane anchoring domain consisting of a right-handed spiral of amphipathic helices (residues 73116) forming a planar motif. Two different computational approaches are used to examine the association of the PGHS-1 membrane anchoring domain with a membrane via the proposed mechanism. The electrostatic contribution to the free energy of solvation is obtained by solving numerically the finite-difference Poisson equation for the protein attached to a membrane represented as a planar slab of low dielectric. The nonpolar cavity formation and van der Waals contributions to the solvation free energy are assumed to be proportional to the water accessible surface area. Based on the optimum position determined from the continuum solvent model, two atomic models of the PGHS-1 anchoring domain associated with an explicit dimyristoylphosphatidylcholine (DMPC) bilayer differing by the thickness of the membrane bilayer were constructed. A total of 2 ns molecular dynamics simulation were performed to study the details of lipid-protein interactions at the microscopic level. In the simulations the lipid hydrocarbon chains interacting with the anchoring domain assume various shapes, suggesting that the plasticity of the membrane is significant. The hydrophobic residues in the membrane side of the helices interact with the hydrophobic membrane core, while the positively charged residues interact with the lipid polar headgroups to stabilize the anchoring of the membrane domain to the upper half of the bilayer. The phosphate headgroup of one DMPC...


Related Articles

  • Lipopeptide detergents designed for the structural study of membrane proteins. McGregor, Clare-Louise; Chen, Lu; Pomroy, Neil C.; Hwang, Peter; Go, Sandy; Chakrabartty, Avijit; Privé, Gilbert G. // Nature Biotechnology;Feb2003, Vol. 21 Issue 2, p171 

    The structural study of membrane proteins requires detergents that can effectively mimic lipid bilayers, and the choice of detergent is often a compromise between detergents that promote protein stability and detergents that form small micelles. We describe lipopeptide detergents (LPDs), a new...

  • Coarse-grain simulations of active molecular machines in lipid bilayers. Huang, Mu-Jie; Kapral, Raymond; Mikhailov, Alexander S.; Chen, Hsuan-Yi // Journal of Chemical Physics;May2013, Vol. 138 Issue 19, p195101 

    A coarse-grain method for simulations of the dynamics of active protein inclusions in lipid bilayers is described. It combines the previously proposed hybrid simulations of bilayers [M.-J. Huang, R. Kapral, A. S. Mikhailov, and H.-Y. Chen, J. Chem. Phys. 137, 055101 (2012)], based on molecular...

  • Setting up and optimization of membrane protein simulations. Faraldo-Gómez, José D.; Smith, Graham R.; Sansom, Mark P. // European Biophysics Journal;2002, Vol. 31 Issue 3, p217 

    In this paper we describe a method for setting up an atomistic simulation of a membrane protein in a hydrated lipid bilayer and report the effect of differing electrostatic parameters on the drift in the protein structure during the subsequent simulation. The method aims to generate a suitable...

  • Effect of monogalactosyldiacylglycerol on the interaction between photosystem II core complex and its antenna complexes in liposomes of thylakoid lipids. Shuang Liu; Zhaohui Hu; Tingyun Kuang; Harald Paulsen // Photosynthesis Research;Mar2009, Vol. 99 Issue 3, p185 

    Abstract  The non-bilayer lipid monogalactosyldiacylglycerol (MGDG) is the most abundant type of lipid in the thylakoid membrane and plays an important role in regulating the structure and function of photosynthetic membrane proteins. In this study, we have reconstituted the isolated major...

  • Regulation of activity of the NHE1 isoform of the Na[sup +] /H[sup +] exchanger.  // Biochemistry & Cell Biology;Oct2002, Vol. 80 Issue 5, p691 

    Presents abstracts on genetics and membrane proteins. 'Cleavage of a Reconstituted GPI-Anchored Membrane Protein by Bacterial PI-specific phospholipase C: Modulation by the properties of the Lipid Bilayer,' by F.J. Sharom and M.T. Letho; 'Aquaporin Water Channels--From Atomic Structure to...

  • Posters 1-1--8-23.  // European Biophysics Journal;2003, Vol. 32 Issue 3, p196 

    Presents several abstracts of articles on biophysics. 'Construction of Polymer-Tethered Phospholipid Bilayers for Protein-Membrane Interaction Studies,' by J. Chopineau; 'Polymer-Liposome Association Induced by Electrostatic Interactions,' by F. Torrens; 'Prodan Fluorescence Influenced by High...

  • Oral presentations.  // European Biophysics Journal;2003, Vol. 32 Issue 3, p163 

    Presents several abstracts on oral presentations delivered during the 3rd European Biophysics Societies Association Congress in 2003. 'Study by PMIRAS and Brewster Angle Microscopy of Phospholipid Bilayer Stabilized at the Air/Water Interface'; 'Confocal and Two-Photon Excitation Techniques...

  • New routes to membrane protein structures. Thomas, Gavin H. // EMBO Reports;Mar2001, Vol. 2 Issue 3, p187 

    This article focuses on methods in membrane protein structure. Membrane proteins are essential for cellular life: they contribute to the multitude of processes whereby cells interact with their environment, generate energy and maintain their cellular milieu and structure. Consequently, about a...

  • Red Blood Cell Shape and Fluctuations: Cytoskeleton Confinement and ATP Activity. Gov, N.; Safran, S. A. // Journal of Biological Physics;Jul2005, Vol. 31 Issue 3/4, p453 

    We review recent theoretical work that analyzes experimental measurements of the shape and fluctuations of red blood cells. Particular emphasis is placed on the role of the cytoskeleton and cell elasticity and we contrast the situation of elastic cells with that of fluid-filled vesicles. In red...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics