| Popis: |
Cell membranes are composed of a great diversity of lipids and proteins. The lipid raft concept suggests that instead of a homogeneous distribution of the membrane components, they are laterally segregated into domains of compositional and functional diversities. The rafts are thought to be functional membrane domains rich in saturated lipids and cholesterol, serving as platforms for signaling and lateral sorting of membrane components. G protein–coupled receptors (GPCRs) are versatile signaling machines that control a large variety of physiological processes. For example, the cyclic adenosine monophosphate (cAMP) signaling pathway used for cellular communication is triggered by GPCRs. Many signaling components in the cAMP pathway have been associated to rafts. The compartmentalization of signaling components to small regions would enable a rapid and accurate activation of the signaling pathways. It is not clear, however, whether GPCRs themselves reside in raft-like domains. GPCRs constitute the largest class of integral membrane proteins and are major drug targets. Therefore, further knowledge on their location in cell membranes could be significant in understanding the signaling processes they trigger and furthermore in the development of drugs acting on them. The aim of this work is to investigate the partitioning of the β2-adrenergic receptor, a characteristic GPCR, in a phase segregated membrane by molecular dynamics simulations, and thus to find out the receptor’s preference for different domains. This is done by systematically placing the receptor in different membrane domains, such as liquid-ordered (Lo) or liquid-disordered (Ld) domains, or in a random distribution of a phase separating lipid mixture. According to the results, the receptor does not completely reside either in the raft-like Lo domain or in the Ld domain. The receptor repeatedly seeks to the Lo/Ld boundary irrespective of the initial location, and creates a special environment around it consisting of cholesterol and Ld-associated unsaturated lipids. |
