6wc5

From Proteopedia

Crystal Structure of a Ternary MEF2B/NKX2-5/myocardin enhancer DNA Complex

PDB ID 6wc5

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Structural highlights

6wc5 is a 10 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MEF2B_HUMAN Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific genes. Activates transcription via this element. May be involved in muscle-specific and/or growth factor-related transcription.

Publication Abstract from PubMed

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.

Crystal Structures of Ternary Complexes of MEF2 and NKX2-5 Bound to DNA Reveal a Disease Related Protein-Protein Interaction Interface.,Lei X, Zhao J, Sagendorf JM, Rajashekar N, Xu J, Dantas Machado AC, Sen C, Rohs R, Feng P, Chen L J Mol Biol. 2020 Sep 4;432(19):5499-5508. doi: 10.1016/j.jmb.2020.07.004. Epub, 2020 Jul 15. PMID:32681840^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lei X, Zhao J, Sagendorf JM, Rajashekar N, Xu J, Dantas Machado AC, Sen C, Rohs R, Feng P, Chen L. Crystal Structures of Ternary Complexes of MEF2 and NKX2-5 Bound to DNA Reveal a Disease Related Protein-Protein Interaction Interface. J Mol Biol. 2020 Sep 4;432(19):5499-5508. doi: 10.1016/j.jmb.2020.07.004. Epub, 2020 Jul 15. PMID:32681840 doi:http://dx.doi.org/10.1016/j.jmb.2020.07.004