Structural analysis of the evolution of steroid specificity in the mineralocorticoid and glucocorticoid receptorsReport as inadecuate




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BMC Evolutionary Biology

, 7:24

First Online: 16 February 2007Received: 08 March 2006Accepted: 16 February 2007

Abstract

BackgroundThe glucocorticoid receptor GR and mineralocorticoid receptor MR evolved from a common ancestor. Still not completely understood is how specificity for glucocorticoids e.g. cortisol and mineralocorticoids e.g. aldosterone evolved in these receptors.

ResultsOur analysis of several vertebrate GRs and MRs in the context of 3D structures of human GR and MR indicates that with the exception of skate GR, a cartilaginous fish, there is a deletion in all GRs, at the position corresponding to Ser-949 in human MR. This deletion occurs in a loop before helix 12, which contains the activation function 2 AF2 domain, which binds coactivator proteins and influences transcriptional activity of steroids. Unexpectedly, we find that His-950 in human MR, which is conserved in the MR in chimpanzee, orangutan and macaque, is glutamine in all teleost and land vertebrate MRs, including New World monkeys and prosimians.

ConclusionEvolution of differences in the responses of the GR and MR to corticosteroids involved deletion in the GR of a residue corresponding to Ser-949 in human MR. A mutation corresponding to His-950 in human MR may have been important in physiological changes associated with emergence of Old World monkeys from prosimians.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2148-7-24 contains supplementary material, which is available to authorized users.

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Author: Michael E Baker - Charlie Chandsawangbhuwana - Noah Ollikainen

Source: https://link.springer.com/article/10.1186/1471-2148-7-24







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