4EGC: Crystal Structure Of Mbp-fused Human Six1 Bound To Human Eya2 Eya Domain

SIX1 interacts with EYA to form a bipartite transcription factor essential for mammalian development. Loss of function of this complex causes branchio-oto-renal (BOR) syndrome, whereas re-expression of SIX1 or EYA promotes metastasis. Here we describe the 2.0-A structure of SIX1 bound to EYA2, which suggests a new DNA-binding mechanism for SIX1 and provides a rationale for the effect of BOR syndrome mutations. The structure also reveals that SIX1 uses predominantly a single helix to interact with EYA. Substitution of a single amino acid in this helix is sufficient to disrupt SIX1-EYA interaction, SIX1-mediated epithelial-mesenchymal transition and metastasis in mouse models. Given that SIX1 and EYA are overexpressed in many tumor types, our data indicate that targeting the SIX1-EYA complex may be a potent approach to inhibit tumor progression in multiple cancer types.
PDB ID: 4EGCDownload
MMDB ID: 107937
PDB Deposition Date: 2012/3/30
Updated in MMDB: 2017/07
Experimental Method:
x-ray diffraction
Resolution: 1.99  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 4EGC: dimeric; determined by author and by software (PISA)
Molecular Components in 4EGC
Label Count Molecule
Proteins (2 molecules)
Maltose-binding Periplasmic Protein, Homeobox Protein Six1 Chimera
Molecule annotation
Eyes Absent Homolog 2(Gene symbol: EYA2)
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB