Ancestral corticoid receptor / aldosterone complex
An ancestral corticoid receptor (AncCR) has been resurrected. Its maximum likelihood sequence was phylogenetically determined from a number of offspring sequences of glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) in vertebrates. After that, it was biochemically synthesized, expressed in cultured cells and its structure determined by x-ray crystallography. The structure of PDB:2Q1H is a complex of the AncCR and aldosterone (Fig. 1). GR are activated by cortisol and regulate stress response, glucose homeostasis, and other functions. MR are activated by aldosterone in tetrapods and by deoxycorticosterone (DOC) in teleosts to control electrolyte homeostasis, kidney and colon function, and other processes. MR are also sensitive to cortisol, though considerably less so than to aldosterone and DOC. The resurrected AncCR has an intermediate property among GRs and MRs, can bind with aldosterone, DOC and cortisol. Thus AncCR structures in complex with aldosterone (xPSSS:2Q1H), DOC (xPSSS:2Q3Y), and cortisol (xPSSS:2Q1V) have been solved at 1.9, 2.0 and 2.4Å resolution, respectively. These three substrates are adrenal steroid hormones.
It is difficult to estimate a functional change which comes from local structural changes based on the sequence similarity. Thus, estimation of evolutionary crucial substitutions and mapping them to protein structures would be fundamental to understand structure-function relationships.
Protein Data Bank (PDB)
Ortlund, E.A. Bridgham, J.T. Redinbo, M.R. Thornton, J.W.; "Crystal structure of an ancient protein: evolution by conformational epistasis."; Science; (2007) 317:1544-1548 PubMed:17702911.
author: Naoya Fujita