PDBsum entry 4s0h

Transcription/DNA

PDB id: 4s0h

Contents

Protein chains

176 a.a.

53 a.a.

DNA/RNA

Waters ×2

PDB id:

4s0h

Name:

Transcription/DNA

Title:

Tbx5 db, nkx2.5 hd, anf DNA complex

Structure:

T-box transcription factor tbx5. Chain: a, e. Fragment: db (unp residues 53-238). Synonym: t-box protein 5. Engineered: yes. Homeobox protein nkx-2.5. Chain: b, f. Fragment: hd (unp residues 142-194). Synonym: cardiac-specific homeobox, homeobox protein csx, homeobox

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tbx5. Expressed in: unidentified. Expression_system_taxid: 32644. Gene: nkx2-5, csx, nkx2.5, nkx2e. Synthetic: yes. Synthetic construct.

Resolution:

2.82Å R-factor: 0.195 R-free: 0.248

Authors:

L.Pradhan

Key ref:

L.Pradhan et al. (2016). Intermolecular Interactions of Cardiac Transcription Factors NKX2.5 and TBX5. Biochemistry, 55, 1702-1710. PubMed id: 26926761 DOI: 10.1021/acs.biochem.6b00171

Date:

31-Dec-14 Release date: 16-Dec-15

Protein chains

Q99593  (TBX5_HUMAN) -  T-box transcription factor TBX5 from Homo sapiens

Seq: 518 a.a.

Struc: 176 a.a.

Protein chains

P52952  (NKX25_HUMAN) -  Homeobox protein Nkx-2.5 from Homo sapiens

Seq: 324 a.a.

Struc: 53 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DNA/RNA chains

T-C-T-C-A-C-A-C-C-T-T-T-G-A-A-G-T-G-G 19 bases

C-C-A-C-T-T-C-A-A-A-G-G-T-G-T-G-A-G-A 19 bases

T-C-T-C-A-C-A-C-C-T-T-T-G-A-A-G-T-G-G 19 bases

C-C-A-C-T-T-C-A-A-A-G-G-T-G-T-G-A-G-A 19 bases

Enzyme reactions

• Enzyme class: Chains A, B, E, F: E.C.?

DOI no: 10.1021/acs.biochem.6b00171

Biochemistry 55:1702-1710 (2016)

PubMed id: 26926761

Intermolecular Interactions of Cardiac Transcription Factors NKX2.5 and TBX5.

L.Pradhan, S.Gopal, S.Li, S.Ashur, S.Suryanarayanan, H.Kasahara, H.J.Nam.

ABSTRACT

Heart development in mammalian systems is controlled by combinatorial interactions of master cardiac transcription factors such as TBX5 and NKX2.5. They bind to promoters/enhancers of downstream targets as homo- or heteromultimeric complexes. They physically interact and synergistically regulate their target genes. To elucidate the molecular basis of the intermolecular interactions, a heterodimer and a homodimer of NKX2.5 and TBX5 were studied using X-ray crystallography. Here we report a crystal structure of human NKX2.5 and TBX5 DNA binding domains in a complex with a 19 bp target DNA and a crystal structure of TBX5 homodimer. The ternary complex structure of NKX2.5 and TBX5 with the target DNA shows physical interactions between the two proteins through Lys158 (NKX2.5), Asp140 (TBX5), and Pro142 (TBX5), residues that are highly conserved in TBX and NKX families across species. Extensive homodimeric interactions were observed between the TBX5 proteins in both crystal structures. In particular, in the crystal structure of TBX5 protein that includes the N-terminal and DNA binding domains, intermolecular interactions were mediated by the N-terminal domain of the protein. The N-terminal domain of TBX5 was predicted to be "intrinsically unstructured", and in one of the two molecules in an asymmetric unit, the N-terminal domain assumes a β-strand conformation bridging two β-sheets from the two molecules. The structures reported here may represent general mechanisms for combinatorial interactions among transcription factors regulating developmental processes.