The cyclophilin component of the unactivated estrogen receptor contains a tetratricopeptide repeat domain and shares identity with p59 (FKBP59).
Using a rapid single-step affinity chromatography procedure we have isolated the unactivated estrogen receptor from bovine uterus. Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western analyses for protein extracts recovered from affinity chromatography of receptor cytosols, either preincubated or untreated with estradiol, suggest a component structure for the intact oligomeric receptor which includes hsp90, hsp70, p59, a 40-kDa cyclophilin-related protein, and an uncharacterized 22-kDa protein species. We have chemically determined the amino acid sequences of eight peptides derived from the 40-kDa component and now report the cloning and primary sequence of a cDNA encoding this protein, which is designated estrogen receptor-binding cyclophilin (ERBC). Homology analyses confirm that ERBC is a new member of the cyclophilin family and contains a C-terminal domain with significant sequence homology to an internal region of p59, a binding protein for the immunosuppressant FK506 (FKBP59). This conserved region includes a 3-unit tetratricopeptide repeat domain bounded at the C terminus by a putative calmodulin binding site. We propose that the tetratricopeptide repeat domain mediates the protein interaction properties of ERBC and p59. Both immunophilins may have important roles in receptor assembly and may represent a new category of ligand- and calcium-dependent modulators of protein function.
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Queen Elizabeth II Medical Centre, Nedlands, Western Australia.
T
T
Ratajczak
A
A
Carrello
P J
PJ
Mark
B J
BJ
Warner
R J
RJ
Simpson
R L
RL
Moritz
A K
AK
House
D000591:Amino Acid Isomerases / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry*; D002417:Cattle; D003001:Cloning, Molecular; D003524:Cyclosporins; D004247:DNA; D005260:Female; D006360:Heat-Shock Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D022021:Tacrolimus Binding Proteins
D002352:Carrier Proteins; D003524:Cyclosporins; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D004247:DNA; D000591:Amino Acid Isomerases; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase