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Structural Determinants of Ligand Binding and Receptor Activation by CC Chemokines

STRUCTURAL DETERMINANTS OF LIGAND BINDING AND RECEPTOR ACTIVATION BY CC CHEMOKINES [Pg.79]

The length and composition of the chemokine N-terminus play a crucial role in this process and can determine whether the ligand-receptor [Pg.79]

Understanding of the molecular basis of chemokine receptor activation has been aided considerably by the determination of the crystal structure of the related GPCR bovine rhodopsin (Palczewski et al., 2000), allowing [Pg.80]

Intracellular signalling by chemokine receptors is thought to occur mainly through Gai proteins, as physiological responses are readily inhibited by preincubation of cells with pertussis toxin, which ADP-ribosylates a cysteine residue in the C-terminus of the Gaj subunit, rendering it non-functional. [Pg.81]

The subsequent signaling events downstream of chemokine-mediated G-protein activation are complicated. It has already been mentioned that signaling events from chemokine receptors are commonly inhibited by pertussis toxin, leading to the assumption that chemokine receptors are Ga linked. One of the most rapid occurrences following chemokine receptor activation is a rise in the intracellular calcium concentration dCa +]i), and this has commonly been used as a measurement for the functional response of receptor activation. Increases in [Ca ] are mediated via the jSy subunit of the G-protein that activates phospholipase CjS, leading to 1) hydrolysis of phosphatidylinositol to IP3 and 2) DAG formation, which respectively induce the release of Ca + from intracellular stores and subsequent activation of PKC. PKC activation is necessary for certain leukocyte responses, such as neutrophil respiratory burst (Li et al., 2000), and it also plays a role in receptor phosphorylation, leading to desensitization and internalization, which will be discussed later. [Pg.83]




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Activation of receptors

Activators determination

Active Ligands

Active receptor

Activity determination

Binding activity

Binding of Ligands

Binding structure

CC chemokine

CC chemokine activities

CC chemokines receptors

Chemokine receptors ligand structure

Chemokines binding

Chemokines ligand structure

Chemokines ligands

Chemokines receptors

Chemokines structures

Determination of structure and

Ligand Binding and Activation

Ligand activated

Ligand structures

Ligand-receptor structures

Ligands ligand structure

Ligands receptor/ligand binding

Receptor activation

Receptor activity

Receptor binding

Receptor ligands

Receptor-ligand binding

Structure activity, and

Structures of ligands

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