PDBsum entry 2ojz

Immune system

PDB id: 2ojz

Contents

Protein chains

218 a.a. *

216 a.a. *

Waters ×20

* Residue conservation analysis

PDB id:

2ojz

Name:

Immune system

Title:

Anti-DNA antibody ed10

Structure:

Fab ed10 light chain. Chain: l, m. Fab ed10 heavy chain. Chain: h, i

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Organism_taxid: 10090

Resolution:

2.73Å R-factor: 0.204 R-free: 0.264

Authors:

R.L.Stanfield,S.Sanguineti,I.A.Wilson,G.De Prat-Gay

Key ref:

S.Sanguineti et al. (2007). Specific recognition of a DNA immunogen by its elicited antibody. J Mol Biol, 370, 183-195. PubMed id: 17512945 DOI: 10.1016/j.jmb.2007.04.046

Date:

15-Jan-07 Release date: 12-Jun-07

Protein chains

A2NHM3  (A2NHM3_MOUSE) -  If kappa light chain (Fragment) from Mus musculus

Seq: 219 a.a.

Struc: 218 a.a.*

Protein chains

A0N7J2  (A0N7J2_9MURI) -  Mc5 VHCH1 (Fragment) from Mus sp

Seq: 219 a.a.

Struc: 216 a.a.*

* PDB and UniProt seqs differ at 72 residue positions (black crosses)

DOI no: 10.1016/j.jmb.2007.04.046

J Mol Biol 370:183-195 (2007)

PubMed id: 17512945

Specific recognition of a DNA immunogen by its elicited antibody.

S.Sanguineti, J.M.Centeno Crowley, M.F.Lodeiro Merlo, M.L.Cerutti, I.A.Wilson, F.A.Goldbaum, R.L.Stanfield, G.de Prat-Gay.

ABSTRACT

DNA recognition by antibodies is a key feature of autoimmune diseases, yet model systems with structural information are very limited. The monoclonal antibody ED-10 recognizes one of the strands of the DNA duplex used in the immunogenic complex. Modifications of the 5' end decrease the binding affinity and short oligonucleotides retain high binding affinity. We determined crystal structures for the Fab bound to a 6-mer oligonucleotide containing the specific sequence that raised the antibody and compared it with the unliganded Fab. Only the first two bases from the 5' end (dTdC) display electron density and we observe four key hydrogen bonds at the interface. The thymine ring is stacked between TrpH50 and TrpH95, and the cytosine ring is packed against TyrL32. Upon DNA binding, TyrH97 and TrpH95 rearrange to allow subnanomolar binding affinity, five orders of magnitude higher than other reported complexes, possibly because of having gone through affinity maturation. This structure represents the first bona fide antibody DNA immunogen complex described in atomic detail.

Selected figure(s)

Figure 4.
Figure 4. Stereo view of the ED-10/DNA combining site. Protein CDR loops, their side-chains, and the DNA are colored as in Figure 2(a). Hydrogen bonds between DNA and Fab are shown as black dotted lines.

Figure 5.
Figure 5. Electrostatic surface representation of Fab ED-10. ±15 kT (a) ED-10 Fab, (b) ED-10 Fab/DNA complex. The CDR H3 residues H96–H98 are shown under the transparent surface to illustrate their rearrangement to form a cavity to allow DNA binding. The representation was produced using GRASP.^56

The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 370, 183-195) copyright 2007.

Figures were selected by an automated process.