6NCM

Crystal structure of the human FOXN3 DNA binding domain in complex with a forkhead-like (FHL) DNA sequence

Summary for 6NCM

• Entry DOI: 10.2210/pdb6ncm/pdb
• Related: 6NCE
• Descriptor: Forkhead box protein N3, DNA (5'-D(*AP*TP*AP*GP*CP*GP*TP*CP*TP*TP*AP*GP*CP*AP*TP*G)-3'), DNA (5'-D(*TP*CP*AP*TP*GP*CP*TP*AP*AP*GP*AP*CP*GP*CP*TP*A)-3'), ... (5 entities in total)
• Functional Keywords: sequence specific dna binding, regulation of transcription dna templated, dna binding transcription factor activity, forkhead, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 33199.00

Authors

Rogers, J.M.,Jarrett, S.M.,Seegar, T.C.,Waters, C.T.,Hallworth, A.N.,Blacklow, S.C.,Bulyk, M.L. (deposition date: 2018-12-11, release date: 2019-02-27, Last modification date: 2023-10-11)

Primary citation

Rogers, J.M.,Waters, C.T.,Seegar, T.C.M.,Jarrett, S.M.,Hallworth, A.N.,Blacklow, S.C.,Bulyk, M.L.
Bispecific Forkhead Transcription Factor FoxN3 Recognizes Two Distinct Motifs with Different DNA Shapes.
Mol. Cell, 74:245-, 2019

PubMed Abstract: Transcription factors (TFs) control gene expression by binding DNA recognition sites in genomic regulatory regions. Although most forkhead TFs recognize a canonical forkhead (FKH) motif, RYAAAYA, some forkheads recognize a completely different (FHL) motif, GACGC. Bispecific forkhead proteins recognize both motifs, but the molecular basis for bispecific DNA recognition is not understood. We present co-crystal structures of the FoxN3 DNA binding domain bound to the FKH and FHL sites, respectively. FoxN3 adopts a similar conformation to recognize both motifs, making contacts with different DNA bases using the same amino acids. However, the DNA structure is different in the two complexes. These structures reveal how a single TF binds two unrelated DNA sequences and the importance of DNA shape in the mechanism of bispecific recognition.

PubMed: 30826165
DOI: 10.1016/j.molcel.2019.01.019

Experimental method

X-RAY DIFFRACTION (2.704 Å)