Allosteric modulation of chemoattractant receptors

• Main Authors: Maria Candida Cesta, Marcello eAllegretti, Massimo eLocati
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2016-05-01
• Series: Frontiers in Immunology
• Subjects: chemoattractant; chemokine receptor; Leukocyte recruitment; functional selectivity; biased signalling
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00170/full

Chemoattractants control selective leukocyte homing via interactions with a dedicated family of related GPCR. Emerging evidence indicates that the signalling activity of these receptors, as for other GPCR, is influenced by allosteric modulators, which interact with the receptor in a binding site distinct from the binding site of the endogenous agonist and modulate the receptor signalling activity in response to the orthosteric ligand. Allosteric modulators have a number of potential advantages over orthosteric agonists/antagonists as therapeutic agents and offer unprecedented opportunities to identify extremely selective drug leads. Here we resume evidence of allosterism in the context of chemoattractant receptors, discussing in particular its functional impact on functional selectivity and probe/concentration dependence of orthosteric ligands activities.