PDBsum entry 3ei3

DNA binding protein

PDB id: 3ei3

Contents

Protein chains

1105 a.a. *

355 a.a. *

Ligands

PG4

Waters ×697

* Residue conservation analysis

PDB id:

3ei3

Name:

DNA binding protein

Title:

Structure of the hsddb1-drddb2 complex

Structure:

DNA damage-binding protein 1. Chain: a. Synonym: hsddb1, damage-specific DNA-binding protein 1, uv-damaged DNA-binding factor, ddb p127 subunit, DNA damage-binding protein a, ddba, uv-damaged DNA-binding protein 1, uv-ddb 1, xeroderma pigmentosum group e-complementing protein, xpce, xpe-binding factor, xpe-bf, hbv x-associated protein 1, xap-1. Engineered: yes. DNA damage-binding protein 2.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ddb1, xap1. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: bti-tn-5b1-4. Expression_system_cell: high five cells. Danio rerio.

Resolution:

2.30Å R-factor: 0.210 R-free: 0.251

Authors:

A.Scrima,N.H.Thoma

Key ref:

A.Scrima et al. (2008). Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex. Cell, 135, 1213-1223. PubMed id: 19109893 DOI: 10.1016/j.cell.2008.10.045

Date:

15-Sep-08 Release date: 20-Jan-09

Protein chain

Q16531  (DDB1_HUMAN) -  DNA damage-binding protein 1 from Homo sapiens

Seq: 1140 a.a.

Struc: 1105 a.a.

Protein chain

Q2YDS1  (DDB2_DANRE) -  DNA damage-binding protein 2 from Danio rerio

Seq: 496 a.a.

Struc: 355 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

DOI no: 10.1016/j.cell.2008.10.045

Cell 135:1213-1223 (2008)

PubMed id: 19109893

Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex.

A.Scrima, R.Konícková, B.K.Czyzewski, Y.Kawasaki, P.D.Jeffrey, R.Groisman, Y.Nakatani, S.Iwai, N.P.Pavletich, N.H.Thomä.

ABSTRACT

Ultraviolet (UV) light-induced pyrimidine photodimers are repaired by the nucleotide excision repair pathway. Photolesions have biophysical parameters closely resembling undamaged DNA, impeding discovery through damage surveillance proteins. The DDB1-DDB2 complex serves in the initial detection of UV lesions in vivo. Here we present the structures of the DDB1-DDB2 complex alone and bound to DNA containing either a 6-4 pyrimidine-pyrimidone photodimer (6-4PP) lesion or an abasic site. The structure shows that the lesion is held exclusively by the WD40 domain of DDB2. A DDB2 hairpin inserts into the minor groove, extrudes the photodimer into a binding pocket, and kinks the duplex by approximately 40 degrees. The tightly localized probing of the photolesions, combined with proofreading in the photodimer pocket, enables DDB2 to detect lesions refractory to detection by other damage surveillance proteins. The structure provides insights into damage recognition in chromatin and suggests a mechanism by which the DDB1-associated CUL4 ubiquitin ligase targets proteins surrounding the site of damage.

Selected figure(s)

Figure 1.
Figure 1. Overall Structure of the DDB1–DDB2–DNA Complex
(A) Ribbon representation of the DDB[dr]–DNA^6-4PP complex: DDB2, green; DDB1-BPA, red; DDB1-BPB, magenta; DDB1-BPC, yellow; DDB1-CTD, gray. The DNA^6-4PP damaged and undamaged strands are depicted in black and gray, respectively.
(B) Ribbon representation of the DDB[dr]–DNA^6-4PP complex rotated by 90° about the vertical axis relative to (A).
(C) Schematic representation of hsDDB1 and drDDB2 with domain boundaries.

Figure 3.
Figure 3. Mechanism of 6-4 Photodimer Recognition
(A) Close-up of the DDB2 hairpin insertion (green) at the lesion with the damaged and undamaged strands depicted in yellow and brown, respectively.
(B) Interaction of DDB2 with the DNA^6-4PP backbone. The backbone of both strands is contacted by an array of positively charged residues crucial for the stabilization of the phosphate backbone compression at the damaged site (D[+1], D[+2]). Parts of the DNA are omitted for clarity.
(C) Close-up of the photodimer binding pocket stabilizing the flipped-out dinucleotide. Contacting residues are shown as stick models in yellow. The pyrimidine ring D[+1] and the pyrimidone ring D[+2] are shown in black and gray, respectively. Parts of the DNA have been omitted for clarity.
(D) Chemical structure of the 6-4 pyrimidine-pyrimidone dimer.
(E) Schematic representation of interactions between DDB2 and DNA^6-4PP (with colors as in A and B).

The above figures are reprinted from an Open Access publication published by Cell Press: Cell (2008, 135, 1213-1223) copyright 2008.

Figures were selected by the author.