4EGC

Crystal Structure of MBP-fused Human Six1 Bound to Human Eya2 Eya Domain

Summary for 4EGC

• Entry DOI: 10.2210/pdb4egc/pdb
• Related PRD ID: PRD_900001
• Descriptor: Maltose-binding periplasmic protein, Homeobox protein SIX1 chimera, Eyes absent homolog 2, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: homeodomain (hd), six domain (sd), eya domain (ed), haloacid dehalogenase (had), transcription factor, co-activator, protein phosphatase, dna binding, fusion protein, nucleus, transcription-hydrolase complex, transcription/hydrolase
• Biological source: Escherichia coli (human); More
• Total number of polymer chains: 2
• Total formula weight: 95895.95

Authors

Zhao, R.,Patrick, A.N. (deposition date: 2012-03-30, release date: 2013-02-27, Last modification date: 2024-02-28)

Primary citation

Patrick, A.N.,Cabrera, J.H.,Smith, A.L.,Chen, X.S.,Ford, H.L.,Zhao, R.
Structure-function analyses of the human SIX1-EYA2 complex reveal insights into metastasis and BOR syndrome.
Nat.Struct.Mol.Biol., 20:447-453, 2013

PubMed Abstract: 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-Å 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.

PubMed: 23435380
DOI: 10.1038/nsmb.2505

Experimental method

X-RAY DIFFRACTION (1.994 Å)