PDBsum entry 2aab

Immune system

PDB id: 2aab

Contents

Protein chains

217 a.a. *

224 a.a. *

Waters ×66

* Residue conservation analysis

PDB id:

2aab

Name:

Immune system

Title:

Structural basis of antigen mimicry in a clinically relevant melanoma antigen system

Structure:

Anti-idiotypic monoclonal antibody (light chain). Chain: l. Anti-idiotypic monoclonal antibody (heavy chain). Chain: h. Fragment: fab fragment

Source:

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

Biol. unit:

Dimer (from PQS)

Resolution:

2.50Å R-factor: 0.236 R-free: 0.297

Authors:

C.-C.Chang,F.G.Hernandez-Guzman,W.Luo,X.Wang,S.Ferrone,D.Ghosh

Key ref:

C.C.Chang et al. (2005). Structural basis of antigen mimicry in a clinically relevant melanoma antigen system. J Biol Chem, 280, 41546-41552. PubMed id: 16227204 DOI: 10.1074/jbc.M507562200

Date:

13-Jul-05 Release date: 25-Oct-05

Protein chain

No UniProt id for this chain

Struc: 217 a.a.

Protein chain

No UniProt id for this chain

Struc: 224 a.a.

DOI no: 10.1074/jbc.M507562200

J Biol Chem 280:41546-41552 (2005)

PubMed id: 16227204

Structural basis of antigen mimicry in a clinically relevant melanoma antigen system.

C.C.Chang, F.G.Hernandez-Guzman, W.Luo, X.Wang, S.Ferrone, D.Ghosh.

ABSTRACT

Although mimics of human tumor antigens are effective immunogens to overcome host unresponsiveness to the nominal antigen, the structural basis of this mimicry remains poorly defined. Therefore, in this study we have characterized the structural basis of the human high molecular weight-melanoma-associated antigen (HMW-MAA) mimicry by the mouse anti-idiotypic (anti-id) monoclonal antibody (mAb) MK2-23. Using x-ray crystallography, we have characterized the three-dimensional structure of the anti-id mAb MK2-23 Fab' and shown that its heavy chain complementarity-determining region (CDR3) (H3) and its light chain CDR1 (L1) are closely associated. These moieties are the source of HMW-MAA mimicry, since they display partial amino acid sequence homology along with a similar structural fold with the HMW-MAA core protein. Furthermore, a 15-residue peptide comprising the H3 loop of anti-id mAb MK2-23 demonstrates HMW-MAA-like in vitro and in vivo reactivity. This peptide in conjunction with the structural data will facilitate the characterization of the effect of the degree of antigen mimicry on the induction of a self-antigen-specific immune response by a mimic.

Selected figure(s)

Figure 2.
FIGURE 2. Crystal structure of an anti-id mAb MK2-23 Fab' fragment at 2. 5 Å resolution shown in ribbon diagram. A, the CDR loops of the light (CDR1L) (L1) (green) and heavy (CDR3H) (H3) (yellow) chains are shown as labeled. The boxed area is shown in stereo images (B), detailing the secondary and tertiary structures of anti-id mAb MK2-23 L1 and H3 and their final electron density maps. Hydrogen bonds are shown by dotted lines.

Figure 3.
FIGURE 3. Three-dimensional alignment of five available anti-id mAb: 409.5.3 (PDB code 1AIF), 6A6 (PDB code 1PG7), E225 (PDB code 1CIC [PDB] ), E5.2 (PDB code 1DVF), and MK2-23 (this study), two anti-anti-id mAb: 131 (PDB code 2CK0) and GH1002 (PDB code 1GHF) and two randomly selected idiotypic mAb: Mopc21 (PDB code 1IGC), and R24 (PDB code 1R24 [PDB] ) by using least squares fitting of the conserved residues.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 41546-41552) copyright 2005.

Figures were selected by an automated process.