3D model of amphioxus steroid receptor complexed with estradiol

The origins of signaling by vertebrate steroids are not fully understood. An important advance was the report that an estrogen-binding steroid receptor [SR] is present in amphioxus, a basal chordate with a similar body plan as vertebrates. To investigate the evolution of estrogen-binding to steroid...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2009-08, Vol.386 (3), p.516-520
Main Authors: Baker, Michael E., Chang, David J.
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Amino Acid Sequence
Amphioxus steroid receptor
Animals
Branchiostoma lanceolatum
Chordata
Chordata - metabolism
ESTRADIOL
Estradiol - chemistry
Estrogen Receptor alpha - chemistry
Estrogen signaling
EVOLUTION
Evolution, Molecular
Humans
Marine
Models, Molecular
Molecular Sequence Data
MUTATIONS
Protein Conformation
RECEPTORS
Receptors, Steroid - chemistry
Steroid receptor evolution
TESTOSTERONE
VERTEBRATES
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Summary:The origins of signaling by vertebrate steroids are not fully understood. An important advance was the report that an estrogen-binding steroid receptor [SR] is present in amphioxus, a basal chordate with a similar body plan as vertebrates. To investigate the evolution of estrogen-binding to steroid receptors, we constructed a 3D model of amphioxus SR complexed with estradiol. This 3D model indicates that although the SR is activated by estradiol, some interactions between estradiol and human ERα are not conserved in the SR, which can explain the low affinity of estradiol for the SR. These differences between the SR and ERα in the steroid-binding domain are sufficient to suggest that another steroid is the physiological regulator of the SR. The 3D model predicts that mutation of Glu-346 to Gln will increase the affinity of testosterone for amphioxus SR and elucidate the evolution of steroid-binding to nuclear receptors.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2009.06.079