skip to content
Dovepress - Open Access to Scientific and Medical Research
View our mobile site

8852

Modularity in receptor evolution: insulin- and glucagon-like peptide modules as binding sites for insulin and glucose in the insulin receptor

Original Research

(1520) Views  (564) Full article downloads

Authors: Robert Root-Bernstein, Jessica Vonck

Published Date July 2010 Volume 2010:3 Pages 87 - 96
DOI: http://dx.doi.org/10.2147/JRLCR.S6737

Robert Root-Bernstein1, Jessica Vonck2

1Department of Physiology, Michigan State University, Missouri, USA; 2College of Human Medicine, Michigan State University, Missouri, USA

Abstract: Dwyer suggested that peptide receptors evolved from self-aggregating peptides. Root-Bernstein extended Dwyer’s theory to include complementary molecules. Insulin is a self-aggregating peptide. Insulin is also complementary (and therefore binds) to glucagon. We have shown previously using similarities searches that the insulin receptor (IR) has several insulin-like and several glucagon-like sequences associated with insulin-binding regions. We demonstrate here that peptides derived from these insulin- and glucagon-like regions bind insulin with up to high-nanomolar affinity, providing experimental evidence for the evolution of the IR from insulin- and glucagon-like modules. Moreover, we demonstrate that insulin itself binds glucose (and cytochalasin B), and that many of the insulin-like regions of the IR (but not the glucagon-like regions of the insulin receptor) do likewise. These data suggest the function of insulin, and of the IR in glucose regulation has been directed by chemical selection for their mutual set of molecular interactions. This model may be generalizable to the evolution of other receptor and transporter systems. The relationship between molecular structure and function within living systems may be highly constrained by selection for molecular complementarity.

Keywords: co-evolution, modular evolution, molecular complementarity, chemical selection, molecular paleontology







Readers of this article also read:

Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors
The role of sigma-1 receptors in the pathophysiology of neuropsychiatric diseases
Overview of the LDL receptor: relevance to cholesterol metabolism and future approaches for the treatment of coronary heart disease
Molecular biocoding of insulin
Effects of extracts from Cordyceps sinensis on M1 muscarinic acetylcholine receptor in vitro and in vivo
Chimeric design, synthesis, and biological assays of a new nonpeptide insulin-mimetic vanadium compound to inhibit protein tyrosine phosphatase 1B
Diabetes management: optimizing roles for nurses in insulin initiation
Steroid response pattern and outcome of pediatric idiopathic nephrotic syndrome: a single-center experience in northwest Iran
Antioxidant oils and Salmonella enterica Typhimurium reduce tumor in an experimental model of hepatic metastasis
Cumulative clinical experience from over a decade of use of levofloxacin in community-acquired pneumonia: critical appraisal and role in therapy