PDBsum entry 4tnt

DNA binding protein/DNA

PDB id: 4tnt

Contents

Protein chains

72 a.a.

DNA/RNA

Metals

_ZN ×4

Waters ×4

PDB id:

4tnt

Name:

DNA binding protein/DNA

Title:

Structure of the human mineralocorticoid receptor in complex with DNA

Structure:

Mineralocorticoid receptor. Chain: a, b. Synonym: mr,nuclear receptor subfamily 3 group c member 2. Engineered: yes. DNA (5'- d( Cp Ap Gp Ap Ap Cp Ap Cp Tp Cp Tp Gp Tp Tp Cp Tp G)-3'). Chain: c. Engineered: yes. DNA (5'-

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: nr3c2, mcr, mlr. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Synthetic construct. Organism_taxid: 32630.

Resolution:

2.39Å R-factor: 0.214 R-free: 0.258

Authors:

W.H.Hudson,E.A.Ortlund

Key ref:

W.H.Hudson et al. (2014). Crystal structure of the mineralocorticoid receptor DNA binding domain in complex with DNA. Plos One, 9, e107000. PubMed id: 25188500 DOI: 10.1371/journal.pone.0107000

Date:

04-Jun-14 Release date: 17-Sep-14

Protein chains

P08235  (MCR_HUMAN) -  Mineralocorticoid receptor from Homo sapiens

Seq: 984 a.a.

Struc: 72 a.a.

DNA/RNA chains

C-A-G-A-A-C-A-C-T-C-T-G-T-T-C-T-G 17 bases

C-A-G-A-A-C-A-G-A-G-T-G-T-T-C-T-G 17 bases

DOI no: 10.1371/journal.pone.0107000

Plos One 9:e107000 (2014)

PubMed id: 25188500

Crystal structure of the mineralocorticoid receptor DNA binding domain in complex with DNA.

W.H.Hudson, C.Youn, E.A.Ortlund.

ABSTRACT

The steroid hormone receptors regulate important physiological functions such as reproduction, metabolism, immunity, and electrolyte balance. Mutations within steroid receptors result in endocrine disorders and can often drive cancer formation and progression. Despite the conserved three-dimensional structure shared among members of the steroid receptor family and their overlapping DNA binding preference, activation of individual steroid receptors drive unique effects on gene expression. Here, we present the first structure of the human mineralocorticoid receptor DNA binding domain, in complex with a canonical DNA response element. The overall structure is similar to the glucocorticoid receptor DNA binding domain, but small changes in the mode of DNA binding and lever arm conformation may begin to explain the differential effects on gene regulation by the mineralocorticoid and glucocorticoid receptors. In addition, we explore the structural effects of mineralocorticoid receptor DNA binding domain mutations found in type I pseudohypoaldosteronism and multiple types of cancer.