Lipid-modulated sequence-specific association of glycophorin A in membranes.
Protein association in lipid membranes is a complex process with thermodynamics directed by a multitude of different factors. Amino-acid sequence is a molecular parameter that affects dimerization as shown by limited directed mutations along the transmembrane domains. Membrane-mediated interactions are also important although details of such contributions remain largely unclear. In this study, we probe directly the free energy of association of Glycophorin A by means of extensive parallel Monte Carlo simulations with recently developed methods and a model that accounts for sequence-specificity while representing lipid membranes faithfully. We find that lipid-induced interactions are significant both at short and intermediate separations. The ability of molecules to tilt in a specific hydrophobic environment extends their accessible interfaces, leading to intermittent contacts during protein recognition. The dimer with the lowest free energy is largely determined by the favorable lipid-induced attractive interactions at the closest distance. Finally, the coarse-grained model employed herein, together with the extensive sampling performed, provides estimates of the free energy of association that are in excellent agreement with existing data.
Janosi
Lorant
L
Department of Chemical and Biomolecular Engineering, University of Houston, Houston, Texas, USA.
Prakash
Anupam
A
Doxastakis
Manolis
M
D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism*; D006021:Glycophorins / Q000737:chemistry* / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D013816:Thermodynamics
D006021:Glycophorins; D008051:Lipid Bilayers; D008563:Membrane Lipids