PDBsum entry 6wc5

Transcription

PDB id: 6wc5

Contents

Protein chains

89 a.a.

55 a.a.

55 a.a.

DNA/RNA

Waters ×3

PDB id:

6wc5

Name:

Transcription

Title:

Crystal structure of a ternary mef2b/nkx2-5/myocardin enhancer DNA complex

Structure:

Myocyte-specific enhancer factor 2b. Chain: a, b, c, d. Synonym: rsrfr2,serum response factor-like protein 2. Engineered: yes. Myocardin enhancer DNA. Chain: e, g. Engineered: yes. Myocardin enhancer DNA. Chain: f, h.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mef2b, xmef2. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic construct. Organism_taxid: 32630.

Resolution:

2.90Å R-factor: 0.207 R-free: 0.251

Authors:

L.Chen,X.Lei

Key ref:

X.Lei et al. (2020). Crystal Structures of Ternary Complexes of MEF2 and NKX2-5 Bound to DNA Reveal a Disease Related Protein-Protein Interaction Interface. J Mol Biol, 432, 5499-5508. PubMed id: 32681840 DOI: 10.1016/j.jmb.2020.07.004

Date:

29-Mar-20 Release date: 22-Jul-20

Protein chains

Q02080  (MEF2B_HUMAN) -  Myocyte-specific enhancer factor 2B from Homo sapiens

Seq: 365 a.a.

Struc: 89 a.a.

Protein chain

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

Seq: 324 a.a.

Struc: 55 a.a.*

Protein chain

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

Seq: 324 a.a.

Struc: 55 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DNA/RNA chains

A-A-G-C-A-C-T-T-T-C-T-T-A-A-A-A-T-A-G-T-G 21 bases

C-A-C-T-A-T-T-T-T-A-A-G-A-A-A-G-T-G-C-T-T 21 bases

A-A-G-C-A-C-T-T-T-C-T-T-A-A-A-A-T-A-G-T-G-G 22 bases

C-C-A-C-T-A-T-T-T-T-A-A-G-A-A-A-G-T-G-C-T-T 22 bases

DOI no: 10.1016/j.jmb.2020.07.004

J Mol Biol 432:5499-5508 (2020)

PubMed id: 32681840

Crystal Structures of Ternary Complexes of MEF2 and NKX2-5 Bound to DNA Reveal a Disease Related Protein-Protein Interaction Interface.

X.Lei, J.Zhao, J.M.Sagendorf, N.Rajashekar, J.Xu, A.C.Dantas Machado, C.Sen, R.Rohs, P.Feng, L.Chen.

ABSTRACT

MEF2 and NKX2-5 transcription factors interact with each other in cardiogenesis and are necessary for normal heart formation. Despite evidence suggesting that these two transcription factors function synergistically and possibly through direct physical interactions, molecular mechanisms by which they interact are not clear. Here we determined the crystal structures of ternary complexes of MEF2 and NKX2-5 bound to myocardin enhancer DNA in two crystal forms. These crystal structures are the first example of human MADS-box/homeobox ternary complex structures involved in cardiogenesis. Our structures reveal two possible modes of interactions between MEF2 and NKX2-5: MEF2 and NKX bind to adjacent DNA sites to recognize DNA in cis; and MEF2 and NKX bind to different DNA strands to interact with each other in trans via a conserved protein-protein interface observed in both crystal forms. Disease-related mutations are mapped to the observed protein-protein interface. Our structural studies provide a starting point to understand and further study the molecular mechanisms of the interactions between MEF2 and NKX2.5 and their roles in cardiogenesis.