PDBsum entry 2a07

Transcription/DNA

PDB id: 2a07

Contents

Protein chains

(+ 0 more) 82 a.a. *

DNA/RNA

Metals

_MG ×6

Waters ×581

* Residue conservation analysis

PDB id:

2a07

Name:

Transcription/DNA

Title:

Crystal structure of foxp2 bound specifically to DNA.

Structure:

5'-d( Ap Ap Cp Tp Ap Tp Gp Ap Ap Ap Cp Ap Ap Ap Tp Tp Tp Tp Cp Cp T)-3'. Chain: a, c. Engineered: yes. Other_details: promoter element of a foxp regulated gene, plus strand. 5'-d( Tp Tp Ap Gp Gp Ap Ap Ap Ap Tp Tp Tp Gp Tp Tp Tp Cp Ap Tp Ap G)-3'. Chain: b, d.

Source:

Synthetic: yes. Other_details: DNA is synthesized by solid phase method. Homo sapiens. Human. Organism_taxid: 9606. Gene: foxp2, cagh44, tnrc10. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Decamer (from PQS)

Resolution:

1.90Å R-factor: 0.222 R-free: 0.244

Authors:

J.C.Stroud,Y.Wu,D.L.Bates,A.Han,K.Nowick,S.Paabo,H.Tong,L.Chen

Key ref:

J.C.Stroud et al. (2006). Structure of the forkhead domain of FOXP2 bound to DNA. Structure, 14, 159-166. PubMed id: 16407075 DOI: 10.1016/j.str.2005.10.005

Date:

16-Jun-05 Release date: 31-Jan-06

Protein chains

O15409  (FOXP2_HUMAN) -  Forkhead box protein P2 from Homo sapiens

Seq: 715 a.a.

Struc: 82 a.a.

DNA/RNA chains

A-A-C-T-A-T-G-A-A-A-C-A-A-A-T-T-T-T-C-C-T 21 bases

T-T-A-G-G-A-A-A-A-T-T-T-G-T-T-T-C-A-T-A-G 21 bases

A-A-C-T-A-T-G-A-A-A-C-A-A-A-T-T-T-T-C-C-T 21 bases

T-T-A-G-G-A-A-A-A-T-T-T-G-T-T-T-C-A-T-A-G 21 bases

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/j.str.2005.10.005

Structure 14:159-166 (2006)

PubMed id: 16407075

Structure of the forkhead domain of FOXP2 bound to DNA.

J.C.Stroud, Y.Wu, D.L.Bates, A.Han, K.Nowick, S.Paabo, H.Tong, L.Chen.

ABSTRACT

FOXP (FOXP1-4) is a newly defined subfamily of the forkhead box (FOX) transcription factors. A mutation in the FOXP2 forkhead domain cosegregates with a severe speech disorder, whereas several mutations in the FOXP3 forkhead domain are linked to the IPEX syndrome in human and a similar autoimmune phenotype in mice. Here we report a 1.9 A crystal structure of the forkhead domain of human FOXP2 bound to DNA. This structure allows us to revise the previously proposed DNA recognition mechanism and provide a unifying model of DNA binding for the FOX family of proteins. Our studies also reveal that the FOXP2 forkhead domain can form a domain-swapped dimer, made possible by a strategic substitution of a highly conserved proline in conventional FOX proteins with alanine in the P subfamily. Disease-causing mutations in FOXP2 and FOXP3 map either to the DNA binding surface or the domain-swapping dimer interface, functionally corroborating the crystal structure.

Selected figure(s)

Figure 6.
Figure 6. Disease Mutations
(A) IPEX mutation Ile363Val in FOXP3. The corresponding residue in FOXP2, Ile530, forms a cascade of van der Waals interactions with Leu527, Leu556, and Trp573 that contribute directly or indirectly to DNA binding.
(B) IPEX mutation Ala384Thr in FOXP3. The corresponding residue Ala551 in FOXP2 on helix H3 packs intimately against Tyr509. The Ala384Thr mutation would bring an extra g-methyl group into a tightly packed protein/DNA interface and disrupt DNA binding.
(C) IPEX mutations Phe371Cys and Phe371Leu in FOXP3. The corresponding residue Phe538 in FOXP2 is critically located at the center of the domain-swapped dimer interface. Mutations of this phenylalanine residue to Cys or even a hydrophobic residue Leu may disrupt dimerization.

The above figure is reprinted by permission from Cell Press: Structure (2006, 14, 159-166) copyright 2006.

Figure was selected by an automated process.