PDBsum entry 1c5d

Immune system

PDB id: 1c5d

Contents

Protein chains

213 a.a. *

214 a.a. *

Waters ×209

* Residue conservation analysis

PDB id:

1c5d

Name:

Immune system

Title:

The crystal structure of the fab fragment of a rat monoclonal antibody against the main immunogenic region of the human muscle acetylcholine receptor

Structure:

Monoclonal antibody against the main immunogenic region of the human muscle acetylcholine receptor. Chain: l, a. Fragment: fab fragment, heavy chain. Monoclonal antibody against the main immunogenic region of the human muscle acetylcholine receptor. Chain: h, b. Fragment: fab fragment, light chain

Source:

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

Biol. unit:

Dimer (from PQS)

Resolution:

2.40Å R-factor: 0.196 R-free: 0.304

Authors:

M.Kontou,D.D.Leonidas,E.H.Vatzaki,P.Tsantili,A.Mamalaki, N.G.Oikonomakos,K.R.Acharya,S.J.Tzartos

Key ref:

M.Kontou et al. (2000). The crystal structure of the Fab fragment of a rat monoclonal antibody against the main immunogenic region of the human muscle acetylcholine receptor. Eur J Biochem, 267, 2389-2397. PubMed id: 10759865 DOI: 10.1046/j.1432-1327.2000.01252.x

Date:

17-Nov-99 Release date: 03-Dec-99

Protein chains

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

Seq: 106 a.a.

Struc: 213 a.a.

Protein chains

P20761  (IGG2B_RAT) -  Ig gamma-2B chain C region from Rattus norvegicus

Seq: 333 a.a.

Struc: 214 a.a.*

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

DOI no: 10.1046/j.1432-1327.2000.01252.x

Eur J Biochem 267:2389-2397 (2000)

PubMed id: 10759865

The crystal structure of the Fab fragment of a rat monoclonal antibody against the main immunogenic region of the human muscle acetylcholine receptor.

M.Kontou, D.D.Leonidas, E.H.Vatzaki, P.Tsantili, A.Mamalaki, N.G.Oikonomakos, K.R.Acharya, S.J.Tzartos.

ABSTRACT

The crystal structure of the Fab fragment of a rat monoclonal antibody, number 192, with a very high affinity (Kd = 0.05 nM) for the main immunogenic region of the human muscle acetylcholine receptor (AChR), has been determined and refined to 2.4 A resolution by X-ray crystallographic methods. The overall structure is similar to a Fab (NC6.8) from a murine antibody, used as a search model in molecular replacement. Structural comparisons with known antibody structures showed that the conformations of the hypervariable regions H1, H2, L1, L2, L3 of Fab192 adopt the canonical structures 1, 1, 2, 1, and 1, respectively. The surface of the antigen-binding site is relatively planar, as expected for an antibody against a large protein antigen, with an accessible area of 2865 A2. Analysis of the electrostatic surface potential of the antigen-binding site shows that the bottom of the cleft formed in the center of the site appears to be negatively charged. The structure will be useful in the rational design of very high affinity humanized mutants of Fab192, appropriate for therapeutic approaches of the model autoimmune disease myasthenia gravis.

Selected figure(s)

Figure 1.
Fig. 1. Stereo diagrams of residues of the light chain of Fab192 in the vicinity of the disulphide bond between Cys23 and Cys88 (a) and residues from the CDR3 loop of the heavy chain (b) and electron densities from 2Fo-Fc maps. The contour levels correspond to 0.13 e·Å^-3 (e, electrons). The figures were produced using the program BOBSCRIPT [43].

Figure 3.
Fig. 3. A schematic diagram showing the spatial arrangement of the two molecules of Fab192 in the asymmetric unit. The first molecule is colored yellow and the second molecule red. The figure was produced using the program O [20].

The above figures are reprinted by permission from the Federation of European Biochemical Societies: Eur J Biochem (2000, 267, 2389-2397) copyright 2000.

Figures were selected by an automated process.