PDBsum entry 2r5z

Transcription/DNA

PDB id: 2r5z

Contents

Protein chains

75 a.a. *

59 a.a. *

DNA/RNA

Waters ×112

* Residue conservation analysis

PDB id:

2r5z

Name:

Transcription/DNA

Title:

Structure of scr/exd complex bound to a DNA sequence derived from the fkh gene

Structure:

DNA (5'- d( Dap Dcp Dtp Dcp Dtp Dap Dap Dgp Dap Dtp Dtp Dap Dap Dtp Dcp Dgp Dg p Dcp Dtp Dg)-3'). Chain: c. Engineered: yes. DNA (5'- d( Dtp Dcp Dap Dgp Dcp Dcp Dgp Dap Dtp Dtp Dap Dap Dtp Dcp Dtp Dtp Da p Dgp Dap Dg)-3'). Chain: d.

Source:

Synthetic: yes. Synthetic construct. Organism_taxid: 32630. Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: scr. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.60Å R-factor: 0.233 R-free: 0.303

Authors:

A.K.Aggarwal,J.M.Passner,R.Jain

Key ref:

R.Joshi et al. (2007). Functional specificity of a Hox protein mediated by the recognition of minor groove structure. Cell, 131, 530-543. PubMed id: 17981120 DOI: 10.1016/j.cell.2007.09.024

Date:

04-Sep-07 Release date: 05-Feb-08

Protein chain

P09077  (SCR_DROME) -  Homeotic protein Sex combs reduced from Drosophila melanogaster

Seq: 417 a.a.

Struc: 75 a.a.*

Protein chain

P40427  (EXD_DROME) -  Homeobox protein extradenticle from Drosophila melanogaster

Seq: 376 a.a.

Struc: 59 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

DNA/RNA chains

A-C-T-C-T-A-A-G-A-T-T-A-A-T-C-G-G-C-T-G 20 bases

T-C-A-G-C-C-G-A-T-T-A-A-T-C-T-T-A-G-A-G 20 bases

DOI no: 10.1016/j.cell.2007.09.024

Cell 131:530-543 (2007)

PubMed id: 17981120

Functional specificity of a Hox protein mediated by the recognition of minor groove structure.

R.Joshi, J.M.Passner, R.Rohs, R.Jain, A.Sosinsky, M.A.Crickmore, V.Jacob, A.K.Aggarwal, B.Honig, R.S.Mann.

ABSTRACT

The recognition of specific DNA-binding sites by transcription factors is a critical yet poorly understood step in the control of gene expression. Members of the Hox family of transcription factors bind DNA by making nearly identical major groove contacts via the recognition helices of their homeodomains. In vivo specificity, however, often depends on extended and unstructured regions that link Hox homeodomains to a DNA-bound cofactor, Extradenticle (Exd). Using a combination of structure determination, computational analysis, and in vitro and in vivo assays, we show that Hox proteins recognize specific Hox-Exd binding sites via residues located in these extended regions that insert into the minor groove but only when presented with the correct DNA sequence. Our results suggest that these residues, which are conserved in a paralog-specific manner, confer specificity by recognizing a sequence-dependent DNA structure instead of directly reading a specific DNA sequence.

Selected figure(s)

Figure 2.
Figure 2. Protein-DNA Contacts
Protein-DNA contacts for the (A) fkh250 and (B) fkh250^con* complexes. The Exd half site is shaded cyan, the Hox half site is shaded red. Hydrogen bonds are represented by solid lines and nonpolar interactions by dotted lines. Interactions involving the protein main chain are underlined. Green circles are visualized water molecules. The fkh250 complex has more water-mediated contacts from residues such as Gln50, which is oriented differently in the two complexes, and Trp-17, which is positioned identically in the two complexes.

Figure 3.
Figure 3. Minor Groove Insertion of Scr Residues His−12 and Arg3 in fkh250
(A) Electron densities for Arg3 and His−12 in the fkh250 complex, based on a simulated annealing Fo-Fc omit map (contoured at 3.0σ).
(B) Details of the His−12–Arg3 interaction and water-mediated interactions with Thy14, Thy29, and Thy30 of fkh250. The red circle marks a water molecule and dotted lines represent putative hydrogen bonds.

The above figures are reprinted from an Open Access publication published by Cell Press: Cell (2007, 131, 530-543) copyright 2007.

Figures were selected by an automated process.