PDBsum entry 4zd3

Immune system

PDB id: 4zd3

Contents

Protein chains

199 a.a.

205 a.a.

Waters ×78

PDB id:

4zd3

Name:

Immune system

Title:

Structure of a transglutaminase 2-specific autoantibody fab fragment

Structure:

679-14-14e06 fab fragment heavy chain. Chain: h. Engineered: yes. 679-14-14e06 fab fragment light chain. Chain: l. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_taxid: 9606

Resolution:

2.40Å R-factor: 0.204 R-free: 0.264

Authors:

X.Chen,B.Dalhus,K.Hnida,R.Iversen,L.M.Sollid

Key ref:

X.Chen et al. (2015). Structural Basis for Antigen Recognition by Transglutaminase 2-specific Autoantibodies in Celiac Disease. J Biol Chem, 290, 21365-21375. PubMed id: 26160175 DOI: 10.1074/jbc.M115.669895

Date:

16-Apr-15 Release date: 22-Jul-15

Protein chain

No UniProt id for this chain

Struc: 199 a.a.

Protein chain

No UniProt id for this chain

Struc: 205 a.a.

DOI no: 10.1074/jbc.M115.669895

J Biol Chem 290:21365-21375 (2015)

PubMed id: 26160175

Structural Basis for Antigen Recognition by Transglutaminase 2-specific Autoantibodies in Celiac Disease.

X.Chen, K.Hnida, M.A.Graewert, J.T.Andersen, R.Iversen, A.Tuukkanen, D.Svergun, L.M.Sollid.

ABSTRACT

Antibodies to the autoantigen transglutaminase 2 (TG2) are a hallmark of celiac disease. We have studied the interaction between TG2 and an anti-TG2 antibody (679-14-E06) derived from a single gut IgA plasma cell of a celiac disease patient. The antibody recognizes one of four identified epitopes targeted by antibodies of plasma cells of the disease lesion. The binding interface was identified by small angle x-ray scattering, ab initio and rigid body modeling using the known crystal structure of TG2 and the crystal structure of the antibody Fab fragment, which was solved at 2.4 Å resolution. The result was confirmed by testing binding of the antibody to TG2 mutants by ELISA and surface plasmon resonance. TG2 residues Arg-116 and His-134 were identified to be critical for binding of 679-14-E06 as well as other epitope 1 antibodies. In contrast, antibodies directed toward the two other main epitopes (epitopes 2 and 3) were not affected by these mutations. Molecular dynamics simulations suggest interactions of 679-14-E06 with the N-terminal domain of TG2 via the CDR2 and CDR3 loops of the heavy chain and the CDR2 loop of the light chain. In addition there were contacts of the framework 3 region of the heavy chain with the catalytic domain of TG2. The results provide an explanation for the biased usage of certain heavy and light chain gene segments by epitope 1-specific antibodies in celiac disease.