PDBsum entry 2c7a

Receptor/DNA

PDB id: 2c7a

Contents

Protein chains

78 a.a. *

DNA/RNA

Metals

_ZN ×4

Waters ×148

* Residue conservation analysis

PDB id:

2c7a

Name:

Receptor/DNA

Title:

Structure of the progesterone receptor-DNA complex

Structure:

Progesterone receptor. Chain: a, b. Fragment: DNA binding domain, residues 399-476. Synonym: pr. Engineered: yes. 5'-d( Cp Cp Ap Gp Ap Ap Cp Ap Gp Tp Tp Tp Gp Tp Tp Cp Tp G)-3'. Chain: c. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606

Biol. unit:

Tetramer (from PDB file)

Resolution:

2.50Å R-factor: 0.203 R-free: 0.246

Authors:

S.C.Roemer,D.C.Donham,L.Sherman,V.H.Pon,D.P.Edwards,M.E.A.Churchill

Key ref:

S.C.Roemer et al. (2006). Structure of the progesterone receptor-deoxyribonucleic acid complex: novel interactions required for binding to half-site response elements. Mol Endocrinol, 20, 3042-3052. PubMed id: 16931575

Date:

19-Nov-05 Release date: 30-Aug-06

Protein chains

P06401  (PRGR_HUMAN) -  Progesterone receptor from Homo sapiens

Seq: 933 a.a.

Struc: 78 a.a.

DNA/RNA chains

C-C-A-G-A-A-C-A-G-T-T-T-G-T-T-C-T-G 18 bases

C-C-A-G-A-A-C-A-A-A-C-T-G-T-T-C-T-G 18 bases

Enzyme reactions

• Enzyme class: E.C.?

Mol Endocrinol 20:3042-3052 (2006)

PubMed id: 16931575

Structure of the progesterone receptor-deoxyribonucleic acid complex: novel interactions required for binding to half-site response elements.

S.C.Roemer, D.C.Donham, L.Sherman, V.H.Pon, D.P.Edwards, M.E.Churchill.

ABSTRACT

The DNA binding domain (DBD) of nuclear hormone receptors contains a highly conserved globular domain and a less conserved carboxyl-terminal extension (CTE). Despite previous observations that the CTEs of some classes of nuclear receptors are structured and interact with DNA outside of the hexanucleotide hormone response element (HRE), there has been no evidence for such a CTE among the steroid receptors. We have determined the structure of the progesterone receptor (PR)-DBD-CTE DNA complex at a resolution of 2.5 A, which revealed binding of the CTE to the minor groove flanking the HREs. Alanine substitutions of the interacting CTE residues reduced affinity for inverted repeat HREs separated by three nucleotides, and essentially abrogated binding to a single HRE. A highly compressed minor groove of the trinucleotide spacer and a novel dimerization interface were also observed. A PR binding site selection experiment revealed sequence preferences in the trinucleotide spacer and flanking DNA. These results, taken together, support the notion that sequences outside of the HREs influence the DNA binding affinity and specificity of steroid receptors.