In a Class of Their Own - RXFP1 and RXFP2 are Unique Members of the LGR Family.

Emma J Petrie,Ashish Sethi,Samantha Lagaida,Paul R Gooley,Ross A D Bathgate

doi:10.3389/fendo.2015.00137

Abstract

The leucine-rich repeat-containing G protein-coupled receptors (LGRs) family consists of three groups: types A, B, and C and all contain a large extracellular domain (ECD) made up of the structural motif – the leucine-rich repeat (LRR). In the LGRs, the ECD binds the hormone or ligand, usually through the LRRs, that ultimately results in activation and signaling. Structures are available for the ECD of type A and B LGRs, but not the type C LGRs. This review discusses the structural features of LRR proteins, and describes the known structures of the type A and B LGRs and predictions that can be made for the type C LGRs. The mechanism of activation of the LGRs is discussed with a focus on the role of the low-density lipoprotein class A (LDLa) module, a unique feature of the type C LGRs. While the LDLa module is essential for activation of the type C LGRs, the molecular mechanism for this process is unknown. Experimental data for the potential interactions of the type C LGR ligands with the LRR domain, the transmembrane domain, and the LDLa module are summarized.

Highlights

The receptors for the peptide hormones H2 relaxin and insulin-like peptide-3 (INSL3) are unique members of the leucine-rich repeat-containing G protein-coupled receptors (LGRs) family [1]
As structural understanding of other members of the LGR family grows, we review the structural knowledge of the LGR family, and examine what is known about ligand interactions at the extracellular domains (ECDs) of the Class C LGRs in comparison to the other members of this diverse family of G protein-coupled receptors (GPCRs)
The LGR family has in common a leucine-rich repeat (LRR) domain that serves as a ligand-binding site

Summary

Frontiers in Endocrinology

The leucine-rich repeat-containing G protein-coupled receptors (LGRs) family consists of three groups: types A, B, and C and all contain a large extracellular domain (ECD) made up of the structural motif – the leucine-rich repeat (LRR). In the LGRs, the ECD binds the hormone or ligand, usually through the LRRs, that results in activation and signaling. Structures are available for the ECD of type A and B LGRs, but not the type C LGRs. This review discusses the structural features of LRR proteins, and describes the known structures of the type A and B LGRs and predictions that can be made for the type C LGRs. The mechanism of activation of the LGRs is discussed with a focus on the role of the low-density lipoprotein class A (LDLa) module, a unique feature of the type C LGRs. While the LDLa module is essential for activation of the type C LGRs, the molecular mechanism for this process is unknown. Experimental data for the potential interactions of the type C LGR ligands with the LRR domain, the transmembrane domain, and the LDLa module are summarized

Introduction

Short annotated name

Ligand affinitya

Structures of LGRs

Conclusion