caa a22 4500 467938539 CHVBK 20180406153005.0 cr unu---uuuuu 170328e20060101xx s 000 0 eng 10.1007/s10822-006-9034-6 doi (NATIONALLICENCE)springer-10.1007/s10822-006-9034-6 Association of transmembrane helices: what determinesassembling of a dimer? [Elektronische Daten] [Roman Efremov, Yana Vereshaga, Pavel Volynsky, Dmitry Nolde, Alexander Arseniev] Summary: Self-association of two hydrophobic α-helices is studied via unrestrained MonteCarlo (MC) simulations in a hydrophobic slab described by an effective potential. The system under study represents two transmembrane (TM) segments of human glycophorin A (GpA), which form homo-dimers in membranes. The influence of TM electrostatic potential, thickness and hydrophobicity degree of lipid bilayer is investigated. It is shown that the membrane environment stabilizes α-helical conformation of GpA monomers, induces their TM insertion and facilitates inter-helical contacts. Head-to-head orientation of the helices is promoted by the voltage difference across the membrane. Subsequent "fine-tuned” assembling of the dimer is mediated by vander Waals interactions. Only the models of dimer, calculated in a hydrophobic slab with applied voltage agree with experimental data, while simulations invacuo or without TM voltage fail to give reasonable results. The moderate structural heterogeneity of GpA dimers (existence of several groups of states with close energies) is proposed to reflect their equilibrium dynamics in membrane-mimics. The calculations performed for GpA mutants G83A and G86L permit rationalization of mutagenesis data for them. The results of MonteCarlo simulations critically depend on the parameters of the membrane model: adequate description of helix association is achieved in the water-cyclohexane-water system with the membrane thickness 30-34Å, while in membranes with different hydrophobicities and thickness unrealistic conformations of the dimer are found. The computational approach permits efficient prediction of TM helical oligomers based solely on the sequences of interacting peptides. Springer Science+Business Media, Inc., 2006 glycophorin A dimer nationallicence implicit membrane nationallicence mutagenesis insilico nationallicence transmembrane nationallicence electrostatic potential nationallicence two-stage model of membrane protein folding nationallicence GpA : hydrophobic segment 69-97 of human glycophorin A nationallicence GpANMR : NMR-derived model of the GpA dimer nationallicence GpANMR-mem : the lowest-energy states of GpANMR in implicit membrane nationallicence HP : helical "hairpin” nationallicence MC : MonteCarlo nationallicence MP : membrane protein nationallicence TM : transmembrane nationallicence Efremov Roman M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, V-437, 117997 GSP, Moscow, Russia aut Vereshaga Yana M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, V-437, 117997 GSP, Moscow, Russia aut Volynsky Pavel M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, V-437, 117997 GSP, Moscow, Russia aut Nolde Dmitry M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, V-437, 117997 GSP, Moscow, Russia aut Arseniev Alexander M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, V-437, 117997 GSP, Moscow, Russia aut Journal of Computer-Aided Molecular Design Springer Netherlands 20/1(2006-01-01), 27-45 0920-654X 20:1<27 2006 20 10822 https://doi.org/10.1007/s10822-006-9034-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10822-006-9034-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Efremov Roman M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, V-437, 117997 GSP, Moscow, Russia aut NATIONALLICENCE 700 1- Vereshaga Yana M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, V-437, 117997 GSP, Moscow, Russia aut NATIONALLICENCE 700 1- Volynsky Pavel M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, V-437, 117997 GSP, Moscow, Russia aut NATIONALLICENCE 700 1- Nolde Dmitry M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, V-437, 117997 GSP, Moscow, Russia aut NATIONALLICENCE 700 1- Arseniev Alexander M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, V-437, 117997 GSP, Moscow, Russia aut NATIONALLICENCE 773 0- Journal of Computer-Aided Molecular Design Springer Netherlands 20/1(2006-01-01), 27-45 0920-654X 20:1<27 2006 20 10822 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer