Ligand-binding extracellular domain

The X-Ray Structure of the Ligand-Binding Extracellular Domain of mGluRl... 

The activity of the cytokine receptors is terminated by protein phosphatases, which hydrolytically cleave the phosphotyrosine residues. Several cytokine receptors are able to lose their ligand-binding extracellular domain by proteolysis (not shown). The extracellular domain then appears in the blood, where it competes for cytokines. This reduces the effective cytokine concentration. 

Avramopoulou V, Mamalaki A, Tzartos, and Socrates J. Soluble, Oligomeric, and Ligand-binding Extracellular Domain of the Human alpha 7 Acetylcholine Receptor Expressed in Yeast Replacement of the Hydrophobic Cysteine Loop by the Hydrophilic Loop of the ACh-binding Protein Enhances Protein Solu-bility./Bio/ Chem 2004 279(37) 38287-38293. 

Receptors permanently linked to an effector consist of proteins with an extracellular ligand-binding receptor domain and a signal-generating effector domain (Fig. 1). Most of these receptors are composed of two to five structurally related or identical subunits. Effectors can be enzymes or ion channels whose activities are stimulated by agonist binding without significant delay. 

Besides cytoplasmic protein kinases, membrane receptors can exert protein kinase activity. These so-called receptor tyrosine kinases (RTK) contain a ligandbinding extracellular domain, a transmembrane motif, and an intracellular catalytic domain with specificity for tyrosine residues. Upon ligand binding and subsequent receptor oligomerization, the tyrosine residues of the intracellular domain become phosphory-lated by the intrinsic tyrosine kinase activity of the receptor [3, 4]. The phosphotyrosine residues ftmction as docking sites for other proteins that will transmit the signal received by the RTK. 

Xanthou G, Wilhams TJ, Pease JE (2003) Molecular characterization of the chemokine receptor CXCR3 evidence for the involvement of distinct extracellular domains in a multi-step model of ligand binding and receptor activation. Eur J Immunol 33 2927-2936 Xia MQ, Hyman BT (1999) Chemokines/chemokine receptors in the central nervous system and Alzheimer s disease. J Neurovirol 5 32-41... 

Data from studies with other GPCRs have highlighted the importance of extracellular cysteines in ligand binding and the maintenance of the conformational integrity of the receptors. There are typically four conserved cysteine residues found on extracellular domains of chemokine receptors (see Figure 1 and Tables 2 and 3) one on the amino-terminus and one on each of the three extracellular loops. It is clear that the cysteines on extracellular loops 1 and 2 form a disulfide bond that is essential for the proper trafficking of the receptors... 

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