Understanding the common themes and diverse roles of the second extracellular loop (ECL2) of the GPCR super-family

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@article{c5d1ddef69404918b381affadd4600b3,
title = "Understanding the common themes and diverse roles of the second extracellular loop (ECL2) of the GPCR super-family",
abstract = "The extracellular loops (ECLs) of G protein-coupled receptors (GPCRs) can bind directly to docked orthosteric or allosteric ligands, they can contain transient contact points for ligand entry into the transmembrane (TM) bundle and they can regulate the activation of the receptor signalling pathways. Of the three ECLs, ECL2 is the largest and most structurally diverse reflecting its functional importance. This has been shown through biochemical techniques and has been supported by the many subsequent crystal structures of GPCRs bound to both agonists and antagonists. ECL2 shares common structural features between (and sometimes across) receptor sub-families and can facilitate ligand entry to the TM core or act directly as a surface of the ligand-binding pocket. Structural similarities seem to underpin common binding mechanisms; however, where these exist, variations in primary sequence ensure ligand-binding specificity. This review will compare current understanding of the structural themes and main functional roles of ECL2 in ligand binding, activation and regulation of the major families of GPCRs.",
keywords = "GPCR , Extracellular loop , Ligand-binding , Receptor activation , Signalling , Family B",
author = "Woolley, {Michael J.} and Alex Conner",
year = "2016",
month = "11",
day = "27",
doi = "10.1016/j.mce.2016.11.023",
language = "English",
journal = "Molecular and Cellular Endocrinology",
issn = "0303-7207",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Understanding the common themes and diverse roles of the second extracellular loop (ECL2) of the GPCR super-family

AU - Woolley, Michael J.

AU - Conner, Alex

PY - 2016/11/27

Y1 - 2016/11/27

N2 - The extracellular loops (ECLs) of G protein-coupled receptors (GPCRs) can bind directly to docked orthosteric or allosteric ligands, they can contain transient contact points for ligand entry into the transmembrane (TM) bundle and they can regulate the activation of the receptor signalling pathways. Of the three ECLs, ECL2 is the largest and most structurally diverse reflecting its functional importance. This has been shown through biochemical techniques and has been supported by the many subsequent crystal structures of GPCRs bound to both agonists and antagonists. ECL2 shares common structural features between (and sometimes across) receptor sub-families and can facilitate ligand entry to the TM core or act directly as a surface of the ligand-binding pocket. Structural similarities seem to underpin common binding mechanisms; however, where these exist, variations in primary sequence ensure ligand-binding specificity. This review will compare current understanding of the structural themes and main functional roles of ECL2 in ligand binding, activation and regulation of the major families of GPCRs.

AB - The extracellular loops (ECLs) of G protein-coupled receptors (GPCRs) can bind directly to docked orthosteric or allosteric ligands, they can contain transient contact points for ligand entry into the transmembrane (TM) bundle and they can regulate the activation of the receptor signalling pathways. Of the three ECLs, ECL2 is the largest and most structurally diverse reflecting its functional importance. This has been shown through biochemical techniques and has been supported by the many subsequent crystal structures of GPCRs bound to both agonists and antagonists. ECL2 shares common structural features between (and sometimes across) receptor sub-families and can facilitate ligand entry to the TM core or act directly as a surface of the ligand-binding pocket. Structural similarities seem to underpin common binding mechanisms; however, where these exist, variations in primary sequence ensure ligand-binding specificity. This review will compare current understanding of the structural themes and main functional roles of ECL2 in ligand binding, activation and regulation of the major families of GPCRs.

KW - GPCR

KW - Extracellular loop

KW - Ligand-binding

KW - Receptor activation

KW - Signalling

KW - Family B

U2 - 10.1016/j.mce.2016.11.023

DO - 10.1016/j.mce.2016.11.023

M3 - Article

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

ER -