ANIONIC PHOSPHOLIPID INTERACTIONS WITH THE POTASSIUM CHANNEL KCSA: SIMULATION STUDIES.

@article{citeulike:406690, abstract = {Molecular dynamics (MD) simulations have been used to unmask details of specific interactions of anionic phospholipids with inter-subunit binding sites on the surface of the bacterial potassium channel KcsA. Crystallographic data on a diacyl glycerol fragment at this site were used to model phosphatidyl ethanolamine (PE), or phosphatidyl glycerol (PG), or phosphatidic acid (PA) at the inter-subunit binding sites. Each of these models of a KcsA-lipid complex was embedded in phosphatidyl choline bilayer and explored in a 20 ns MD simulation. H-bond analysis revealed that in terms of lipid/protein interactions PA > PG >> PE and revealed how anionic lipids (PG and PA) bind to a site provided by two key arginine residues (R64 and R89) at the interface between adjacent subunits. A 27 ns simulation was performed in which KcsA (without any lipids initially modelled at the R64/R89 sites) was embedded in a PE/PG bilayer. There was a progressive specific increase over the course of the simulation in the number of H-bonds of PG with KcsA. Furthermore, two specific PG binding events at R64/R89 sites were observed. The phosphate oxygen atoms of bound PG formed H-bonds to the guanidinium group of R89, whilst the terminal glycerol H-bonded to R64. Overall, this study suggests that simulations can help identify and characterise sites for specific lipid interactions on a membrane protein surface.}, address = {Univ of Oxford.}, author = {Deol, Sundeep S S. and Domene, Carmen and Bond, Peter J J. and Sansom, Mark S P S. }, citeulike-article-id = {406690}, doi = {http://dx.doi.org/10.1529/biophysj.105.071407}, issn = {0006-3495}, journal = {Biophys J}, keywords = {channel, interaction, kcsa, md, protein-lipid, simulations}, month = {November}, posted-at = {2005-11-23 20:50:42}, priority = {2}, title = {ANIONIC PHOSPHOLIPID INTERACTIONS WITH THE POTASSIUM CHANNEL KCSA: SIMULATION STUDIES.}, url = {http://dx.doi.org/10.1529/biophysj.105.071407}, year = {2005} }

TY - JOUR ID - citeulike:406690 L3 - citeulike-article-id:406690 N2 - Molecular dynamics (MD) simulations have been used to unmask details of specific interactions of anionic phospholipids with inter-subunit binding sites on the surface of the bacterial potassium channel KcsA. Crystallographic data on a diacyl glycerol fragment at this site were used to model phosphatidyl ethanolamine (PE), or phosphatidyl glycerol (PG), or phosphatidic acid (PA) at the inter-subunit binding sites. Each of these models of a KcsA-lipid complex was embedded in phosphatidyl choline bilayer and explored in a 20 ns MD simulation. H-bond analysis revealed that in terms of lipid/protein interactions PA > PG >> PE and revealed how anionic lipids (PG and PA) bind to a site provided by two key arginine residues (R64 and R89) at the interface between adjacent subunits. A 27 ns simulation was performed in which KcsA (without any lipids initially modelled at the R64/R89 sites) was embedded in a PE/PG bilayer. There was a progressive specific increase over the course of the simulation in the number of H-bonds of PG with KcsA. Furthermore, two specific PG binding events at R64/R89 sites were observed. The phosphate oxygen atoms of bound PG formed H-bonds to the guanidinium group of R89, whilst the terminal glycerol H-bonded to R64. Overall, this study suggests that simulations can help identify and characterise sites for specific lipid interactions on a membrane protein surface. JF - Biophys J SN - 0006-3495 AD - Univ of Oxford. TI - ANIONIC PHOSPHOLIPID INTERACTIONS WITH THE POTASSIUM CHANNEL KCSA: SIMULATION STUDIES. KW - channel KW - interaction KW - kcsa KW - md KW - protein-lipid KW - simulations AU - Deol, Sundeep S AU - Domene, Carmen AU - Bond, Peter J AU - Sansom, Mark S P PY - 2005/11/04/ UR - http://dx.doi.org/10.1529/biophysj.105.071407 ER -