Structure of the human FOXO4-DBD-DNA complex at 1.9 A resolution reveals new details of FOXO binding to the DNA

0354847 - ÚMG 2011 RIV DK eng J - Journal Article
Bouřa, E. - Řežábková, L. - Brynda, Jiří - Obšilová, Veronika - Obšil, T.
Structure of the human FOXO4-DBD-DNA complex at 1.9 A resolution reveals new details of FOXO binding to the DNA.
Acta Crystallographica Section D-Biological Crystallography. Roč. 66, č. 12 (2010), s. 1351-1357. ISSN 0907-4449
R&D Projects: GA AV ČR(CZ) IAA501110801; GA MŠMT(CZ) LC554
Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50110509
Keywords : transcription factor AFX * posttranslational modification * specificity
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 6.326, year: 2010

Here, the 1.9 A resolution crystal structure of the DNA-binding domain of human FOXO4 (FOXO4-DBD) bound to a 13 bp DNA duplex containing a FOXO consensus binding sequence is reported. The structure shows a similar recognition of the core sequence as has been shown for two other FOXO proteins. Helix H3 is docked into the major groove and provides all of the base-specific contacts, while the N-terminus and wing W1 make additional contacts with the phosphate groups of DNA. In contrast to other FOXO-DBD-DNA structures, the loop between helices H2 and H3 has a different conformation and participates in DNA binding. In addition, the structure of the FOXO4-DBD-DNA complex suggests that both direct water-DNA base contacts and the unique water-DNA base contacts and the unique water-network interactions contribute to FOXO-DBD binding to the DNA in a sequence-specific manner.
Permanent Link: http://hdl.handle.net/11104/0006279