title: Hydrophobic cluster analysis (HCA) of the hormone-binding domain of receptor proteins.
abstract: A new technique of protein sequence analysis, namely, Hydrophobic Cluster Analysis (HCA), has been used to align and compare the sequences of proteins belonging to the receptor superfamily (steroid, thyroid hormone and retinoic acid receptors) and serpin superfamily (corticosteroid binding globulin (CBG) and alpha 1-antitrypsin (alpha 1-AT]. By matching up clusters of hydrophobic amino-acids that oftenmost correspond to identifiable secondary structures (alpha-helices, beta-strands etc.), it has been possible to deduce the following information on the secondary structures of these proteins: CBG is structurally related to alpha 1-AT (HCA score greater than 80%), the structures of the hormone-binding domains of the steroid receptors that bind 3-keto-delta 4-steroids are closely interrelated (greater than 80%) but less closely related to that of the estrogen receptor (ER) (approximately 75%), vitamin D, retinoic acid and thyroid hormone receptors are structurally closely related (greater than or equal to 80%). Their secondary structures are, however, also related to that of the steroid receptors (approximately 70%), and a high degree of analogy exists between the structures of serpins and of the hormone-binding domains of members of the steroid superfamily (60-70%). HCA has clearly shown that a previous local sequence alignment of the estrogen receptor with other steroid receptors and cytochromes P450 has to be reconsidered. The published consensus steroid binding sequence previously identified in cytochromes is in fact 80 amino-acids upstream from its previously defined position. Other regions of contiguous sequence identity have also been identified which may be involved in the hydrophobic core of the protein or in steroid binding. Their positions have been indicated using the crystal structure of alpha 1-AT as a model.
authors.affiliation: Laboratoire de Minéralogie-Cristallographie, CNRS URA 09, Université Pierre et Marie Curie, Paris, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Mornon
authors.forename: V
authors.initials: V
authors.lastname: Bissery
authors.forename: C
authors.initials: C
authors.lastname: Gaboriaud
authors.forename: A
authors.initials: A
authors.lastname: Thomas
authors.forename: T
authors.initials: T
authors.lastname: Ojasoo
authors.forename: J P
authors.initials: JP
authors.lastname: Raynaud
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D008961:Models, Structural; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid
chemical_list: D011956:Receptors, Cell Surface; D011987:Receptors, Steroid