PDBsum entry 1fn4

Immune system

PDB id: 1fn4

Contents

Protein chains

211 a.a. *

218 a.a. *

Waters ×136

* Residue conservation analysis

PDB id:

1fn4

Name:

Immune system

Title:

Crystal structure of fab198, an efficient protector of acetylcholine receptor against myasthenogenic antibodies

Structure:

Monoclonal antibody against acetylcholine receptor. Chain: a, c. Monoclonal antibody against acetylcholine receptor. Chain: b, d

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Organism_taxid: 10116

Biol. unit:

Dimer (from PQS)

Resolution:

2.80Å R-factor: 0.198 R-free: 0.294

Authors:

K.Poulas,E.Eliopoulos,E.Vatzaki,J.Navaza,M.Kontou

Key ref:

K.Poulas et al. (2001). Crystal structure of Fab198, an efficient protector of the acetylcholine receptor against myasthenogenic antibodies. Eur J Biochem, 268, 3685-3693. PubMed id: 11432734 DOI: 10.1046/j.1432-1327.2001.02274.x

Date:

21-Aug-00 Release date: 26-Sep-01

Protein chains

P01835  (KACB_RAT) -  Ig kappa chain C region, B allele from Rattus norvegicus

Seq: 106 a.a.

Struc: 211 a.a.*

Protein chains

P20760  (IGG2A_RAT) -  Ig gamma-2A chain C region from Rattus norvegicus

Seq: 322 a.a.

Struc: 218 a.a.*

* PDB and UniProt seqs differ at 14 residue positions (black crosses)

DOI no: 10.1046/j.1432-1327.2001.02274.x

Eur J Biochem 268:3685-3693 (2001)

PubMed id: 11432734

Crystal structure of Fab198, an efficient protector of the acetylcholine receptor against myasthenogenic antibodies.

K.Poulas, E.Eliopoulos, E.Vatzaki, J.Navaza, M.Kontou, N.Oikonomakos, K.R.Acharya, S.J.Tzartos.

ABSTRACT

The crystal structure of the Fab fragment of the rat monoclonal antibody 198, with protective activity for the main immunogenic region of the human muscle acetylcholine receptor against the destructive action of myasthenic antibodies, has been determined and refined to 2.8 A resolution by X-ray crystallographic methods. The mouse anti-lysozyme Fab D1.3 was used as a search model in molecular replacement with the AMORE software. The complementarity determining regions (CDR)-L2, CDR-H1 and CDR-H2 belong to canonical groups. Loops CDR-L3, CDR-H2 and CDR-H3, which seem to make a major contribution to binding, were analyzed and residues of potential importance for antigen-binding are examined. The antigen-binding site was found to be a long crescent-shaped crevice. The structure should serve as a model in the rational design of very high affinity humanized mutants of Fab198, appropriate for therapeutic approaches in the model autoimmune disease myasthenia gravis.

Selected figure(s)

Figure 1.
Fig. 1. Ribbon representation of the Fab198 molecule. The molecule exhibits the typical immunoglobulin fold. The CDRs are shown in bold. (A) The molecule is shown with the variable chains (V[L]–V[H]) at the top and the constant (C[L]–C[H]) at the bottom. (B) View from the top of the molecule showing the access to the binding crevice (as in Fig. 5 Go-). The figure was prepared with MOLSCRIPT [41].

Figure 5.
Fig. 5. Top view of the antigen-binding site of the Fab198 molecule in stereo. The binding crevice is formed by residues of V[H] (in red) and V[L] (in blue). The important interacting residues are labeled in their respective colours. Black lines represent the Ca trace of VH and VL. CDRs (Ca atoms only) are represented by thick black lines and labeled (L1-L3, H1-H3). This view corresponds to Fig. 1B Go-and Fig. 6B Go-. The drawing was prepared with MOLSCRIPT [41].

The above figures are reprinted by permission from the Federation of European Biochemical Societies: Eur J Biochem (2001, 268, 3685-3693) copyright 2001.

Figures were selected by an automated process.