PDBsum entry: 1a28

Progesterone receptor

PDB id: 1a28

Contents

Protein chains

251 a.a. *

Ligands

STR ×2

Waters ×180

* Residue conservation analysis

PDB id:

1a28

Name:

Progesterone receptor

Title:

Hormone-bound human progesterone receptor ligand-binding domain

Structure:

Progesterone receptor. Chain: a, b. Fragment: ligand binding domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: t47-d. Gene: pgr. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Other_details: breast cancer

Resolution:

1.80Å R-factor: 0.191 R-free: 0.227

Authors:

P.B.Sigler,S.P.Williams

Key ref:

S.P.Williams and P.B.Sigler (1998). Atomic structure of progesterone complexed with its receptor. Nature, 393, 392-396. PubMed id: 9620806 DOI: 10.1038/30775

Date:

19-Jan-98 Release date: 15-Jul-98

Protein chains

P06401  (PRGR_HUMAN) -  Progesterone receptor

Seq: 933 a.a.

Struc: 251 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: nucleus (1 term)
• Biological process: regulation of transcription, DNA-dependent (1 term)
• Biochemical function: DNA binding (4 terms)

DOI no: 10.1038/30775

Nature 393:392-396 (1998)

PubMed id: 9620806

Atomic structure of progesterone complexed with its receptor.

S.P.Williams, P.B.Sigler.

ABSTRACT

The physiological effects of progestins are mediated by the progesterone receptor, a member of the steroid/nuclear receptor superfamily. As progesterone is required for maintenance of pregnancy, its receptor has been a target for pharmaceuticals. Here we report the 1.8 A crystal structure of a progesterone-bound ligand-binding domain of the human progesterone receptor. The nature of this structure explains the receptor's selective affinity for progestins and establishes a common mode of recognition of 3-oxy steroids by the cognate receptors. Although the overall fold of the progesterone receptor is similar to that found in related receptors, the progesterone receptor has a quite different mode of dimerization. A hormone-induced stabilization of the carboxy-terminal secondary structure of the ligand-binding domain of the progesterone receptor accounts for the stereochemistry of this distinctive dimer, explains the receptor's characteristic pattern of ligand-dependent protease resistance and its loss of repression, and indicates how the anti-progestin RU486 might work in birth control. The structure also indicates that the analogous 3-keto-steroid receptors may have a similar mechanism of action.

Selected figure(s)

Figure 2.
Figure 2 The progesterone-binding pocket. a, Stereo view of the electron density (sigmaA weighted 2F[o]-F[c] at 1.8 Å resolution) of the bound progesterone and surrounding residues contoured at 1.7 superimposed on the refined model. b, space-filling CPK representation of the hormone-binding pocket; carbon, nitrogen and oxygen atoms are grey, blue and red, respectively. Bound progesterone carbon atoms are cyan and oxygen atoms are green. c, Hydrogen-bonding network that serves as the specificity determinant for the 3-oxy function of progesterone. Hydrogen-bond lengths are in Å. Dashed lines indicate the connectivity of residues 777 and 778. The amido-keto interaction is predicted on the basis of the structure of the ER LBD complexes and sequence homology6. d, Interactions between the PR LBD and bound progesterone (centre). Hydrogen bonds are indicated by solid arrows, and van der Waals contacts (4 Å cutoff) by dashed lines.

Figure 3.
Figure 3 Comparison of the PR LBD and RXR LBD dimers. Dashed ends of RXR indicate truncation of the C-terminal five amino acids. Residues in the PR LBD that form the interface are shown at the top. Dashed lines at the top indicate van der Waals contacts (4 Å cutoff), and arrows indicate hydrogen bonds. There is also a van der Waals contact between residues Ala 922 and Leu 921.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (1998, 393, 392-396) copyright 1998.

Figures were selected by an automated process.