A model for the determination of the 3D-spatial distribution of the functions of the hormone-binding domain of receptors that bind 3-keto-4-ene steroids.
A method of comparing the hydrophobic clusters of proteins (hydrophobic cluster analysis, HCA) has revealed that the 3D-folding pattern of the hormone-binding domain (HBD) of steroid hormone receptors (SHRs) may have an unexpectedly high degree of analogy with the known 3D-crystal structures of proteins belonging to the serine proteinase inhibitor (SERPIN) superfamily, e.g. alpha 1-antitrypsin and ovalbumin. The present paper briefly reviews some of the biochemical evidence that supports the structural validity of the SERPIN model and shows how the model can be used to establish hypothetical 3D-locations for functions attributed to different amino-acids or peptide sequences of the HBD: i.e. heat-shock protein binding, transcription activation, phosphorylation, steroid binding, but also ATP-binding. Indeed, the model has enabled the identification of a Rossmann-fold in SHRs that might bind ATP. Visualization of all these functions should help to interpret the chain of concerted events induced by steroid binding.
Lemesle-Varloot
L
L
Laboratoire de Minéralogie-Cristallographie, C.N.R.S. URA 09, Universités Paris, France.
Ojasoo
T
T
Mornon
J P
JP
Raynaud
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002645:Chickens; D002872:Chromosome Deletion; D003198:Computer Simulation; D004220:Disulfides / Q000032:analysis; D006801:Humans; D007664:Ketosteroids / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011965:Receptors, Glucocorticoid / Q000737:chemistry; D011980:Receptors, Progesterone / Q000737:chemistry / Q000235:genetics; D011987:Receptors, Steroid / Q000737:chemistry* / Q000378:metabolism; D015843:Serpins / Q000737:chemistry*; D012984:Software; D013379:Substrate Specificity; D014158:Transcription, Genetic
D004220:Disulfides; D007664:Ketosteroids; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D011987:Receptors, Steroid; D015843:Serpins