Premium
Structural Basis of Allosteric Ligand–Receptor Interactions in the Insulin/Relaxin Peptide Family
Author(s) -
De Meyts Pierre,
Gauguin Lisbeth,
Svendsen Angela Manegold,
Sarhan Mazen,
Knudsen Louise,
Nøhr Jane,
Kiselyov Vladislav V.
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.03837.x
Subject(s) - relaxin , g protein coupled receptor , receptor , insulin receptor , allosteric regulation , grb10 , biology , receptor tyrosine kinase , insulin receptor substrate , insulin , microbiology and biotechnology , chemistry , biochemistry , endocrinology , insulin resistance
The insulin/relaxin superfamily of peptide hormones comprises 10 members in humans. The three members of the insulin‐related subgroup bind to receptor tyrosine kinases (RTKs), while four of the seven members of the relaxin‐like subgroup are now known to bind to G‐protein‐coupled receptors (GPCRs), the so‐called relaxin family peptide receptors (RXFPs). Both systems have a long evolutionary history and play a critical role in fundamental biological processes, such as metabolism, growth, survival and longevity, and reproduction. The structural biology and ligand‐binding kinetics of the insulin and insulin‐like growth factor I receptors have been studied in great detail, culminating in the recent crystal structure of the insulin receptor extracellular domain. Some of the fundamental properties of these receptors, including constitutive dimerization and negative cooperativity, have recently been shown to extend to other RTKs and GPCRs, including RXFPs, confirming kinetic observations made over 30 years ago.