PDBsum entry 3co7

Transcription/DNA

PDB id: 3co7

Contents

Protein chains

87 a.a. *

DNA/RNA

Waters ×4

* Residue conservation analysis

PDB id:

3co7

Name:

Transcription/DNA

Title:

Crystal structure of foxo1 dbd bound to dbe2 DNA

Structure:

DNA (5'- d( Dtp Dcp Dtp Dtp Dgp Dtp Dtp Dtp Dap Dcp Dap Dtp Dtp Dtp Dtp Dg)- 3'). Chain: a, d. Engineered: yes. DNA (5'- d( Dcp Dap Dap Dap Dap Dtp Dgp Dtp Dap Dap Dap Dcp Dap Dap Dgp Da)- 3'). Chain: b, e.

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Gene: foxo1, fkhr, foxo1a. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.91Å R-factor: 0.267 R-free: 0.276

Authors:

M.M.Brent,R.Anand,R.Marmorstein

Key ref:

M.M.Brent et al. (2008). Structural basis for DNA recognition by FoxO1 and its regulation by posttranslational modification. Structure, 16, 1407-1416. PubMed id: 18786403 DOI: 10.1016/j.str.2008.06.013

Date:

27-Mar-08 Release date: 16-Sep-08

Protein chains

Q12778  (FOXO1_HUMAN) -  Forkhead box protein O1 from Homo sapiens

Seq: 655 a.a.

Struc: 87 a.a.

DNA/RNA chains

T-C-T-T-G-T-T-T-A-C-A-T-T-T-T-G 16 bases

C-A-A-A-A-T-G-T-A-A-A-C-A-A-G-A 16 bases

T-C-T-T-G-T-T-T-A-C-A-T-T-T-T-G 16 bases

C-A-A-A-A-T-G-T-A-A-A-C-A-A-G-A 16 bases

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/j.str.2008.06.013

Structure 16:1407-1416 (2008)

PubMed id: 18786403

Structural basis for DNA recognition by FoxO1 and its regulation by posttranslational modification.

M.M.Brent, R.Anand, R.Marmorstein.

ABSTRACT

FoxO transcription factors regulate the transcription of genes that control metabolism, cellular proliferation, stress tolerance, and possibly life span. A number of posttranslational modifications within the forkhead DNA-binding domain regulate FoxO-mediated transcription. We describe the crystal structures of FoxO1 bound to three different DNA elements and measure the change in FoxO1-DNA affinity with acetylation and phosphorylation. The structures reveal additional contacts and increased DNA distortion for the highest affinity DNA site. The flexible wing 2 region of the forkhead domain was not observed in the structures but is necessary for DNA binding, and we show that p300 acetylation in wing 2 reduces DNA affinity. We also show that MST1 phosphorylation of FoxO1 prevents high-affinity DNA binding. The observation that FoxO-DNA affinity varies between response elements and with posttranslational modifications suggests that modulation of FoxO-DNA affinity is an important component of FoxO regulation in health and misregulation in disease.

Selected figure(s)

Figure 3.
Figure 3. Schematic Showing FoxO1 DBD Interactions with IRE and DBE1 DNA Sequences
(A and B) Differences in hydrogen bonding between the DBE and IRE sequences are highlighted in green. Bases that are contacted directly or through water-mediated interactions are shaded. Phosphates that are contacted directly or through water-mediated interactions are highlighted in red.

Figure 4.
Figure 4. Binding of FoxO1 DBD and Truncation Mutants to Cognate DNA Sites
(A–D) EMSA binding studies to IRE and DBE2 DNA using C-terminally truncated FoxO1 DBD constructs.

The above figures are reprinted from an Open Access publication published by Cell Press: Structure (2008, 16, 1407-1416) copyright 2008.

Figures were selected by an automated process.