科研之友
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摘要
Several herpes- and poxviruses have captured chemokine receptors from their hosts and modified these to their own benefit. The human and viral chemokine receptors belong to class A 7 transmembrane (TM) receptors which are characterized by several structural motifs like the DRY-motif in TM3 and the C-terminal tail. In the DRY-motif, the arginine residue serves important purposes by being directly involved in G protein coupling. Interestingly, among the viral receptors there is a greater diversity in the DRY-motif compared to their endogenous receptor homologous. The C-terminal receptor tail constitutes another regulatory region that through a number of phosphorylation sites is involved in signaling, desensitization, and internalization. Also this region is more variable among virus-encoded 7TM receptors compared to human class A receptors. In this review we will focus on these two structural motifs and discuss their role in viral 7TM receptor signaling compared to their endogenous counterparts. 1. Introduction Seven transmembrane (7TM) receptors constitute the largest superfamily of membrane proteins and function as important mediators of extracellular signals to intracellular responses. The chemical diversity of the endogenous ligands is tremendous ranging from small simple chemical entities like photons, ions, and nucleotides, to more complex small ligands like monoamines and peptides, and larger proteins, glycoproteins, and lipids. The 7TM receptors are divided into five classes of which class A or rhodopsin-like receptors is the dominating class [1]. The receptors are characterized by seven membrane-spanning -helices as well as coupling to G proteins; hence, the name is G protein coupled receptors (GPCRs). (In this review we will use the term 7TM receptors instead of GPCRs as these receptors also signal trough non-G protein-dependent pathways, like 汕-arrestin-mediated signaling [2].) Signaling by 7TM receptors through G proteins leads to, for example, either inhibition (G汐i) or activation (G汐s) of adenylyl cyclase and cAMP production, activation of phospholipase C with inositol triphosphate turnover (G汐q), or activation of RhoGEF (G汐12/13) depending on which G protein the receptor is activating [3]. Furthermore, the G汕污 subunit is also involved in signaling and the 7TM receptors also signal via G protein-independent pathways like MAP-kinase activation-mediated by -arrestins [4]. Despite the structural diversity in the repertoire of the endogenous 7TM receptor agonists, the conformational changes that occur upon receptor activation are believed to be
