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PDBsum entry 6wc5
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Transcription
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PDB id
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6wc5
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References listed in PDB file
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Key reference
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Title
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Crystal structures of ternary complexes of mef2 and nkx2-5 bound to DNA reveal a disease related protein-Protein interaction interface.
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Authors
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X.Lei,
J.Zhao,
J.M.Sagendorf,
N.Rajashekar,
J.Xu,
A.C.Dantas machado,
C.Sen,
R.Rohs,
P.Feng,
L.Chen.
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Ref.
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J Mol Biol, 2020,
432,
5499-5508.
[DOI no: ]
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PubMed id
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Abstract
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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.
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