PDBsum entry 3r08

Immune system

PDB id: 3r08

Contents

Protein chains

213 a.a.

216 a.a.

82 a.a.

PDB id:

3r08

Name:

Immune system

Title:

Crystal structure of mouse cd3epsilon in complex with antibody 2c11 fab

Structure:

Mouse anti-mouse cd3epsilon antibody 2c11 light chain. Chain: l. Fragment: unp residues 22-100. Engineered: yes. Mouse anti-mouse cd3epsilon antibody 2c11 heavy chain. Chain: h. Engineered: yes. T-cell surface glycoprotein cd3 epsilon chain. Chain: e.

Source:

Cricetulus migratorius. Organism_taxid: 10032. Cell: hybridoma. Mouse. Gene: cd3e. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell: ovary cells

Resolution:

4.10Å R-factor: 0.224 R-free: 0.277

Authors:

D.A.Shore,X.Zhu,I.A.Wilson

Key ref:

R.A.Fernandes et al. (2012). T cell receptors are structures capable of initiating signaling in the absence of large conformational rearrangements. J Biol Chem, 287, 13324-13335. PubMed id: 22262845

Date:

07-Mar-11 Release date: 25-Jan-12

Protein chain

No UniProt id for this chain

Struc: 213 a.a.

Protein chain

No UniProt id for this chain

Struc: 216 a.a.

Protein chain

P22646  (CD3E_MOUSE) -  T-cell surface glycoprotein CD3 epsilon chain from Mus musculus

Seq: 189 a.a.

Struc: 82 a.a.*

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

J Biol Chem 287:13324-13335 (2012)

PubMed id: 22262845

T cell receptors are structures capable of initiating signaling in the absence of large conformational rearrangements.

R.A.Fernandes, D.A.Shore, M.T.Vuong, C.Yu, X.Zhu, S.Pereira-Lopes, H.Brouwer, J.A.Fennelly, C.M.Jessup, E.J.Evans, I.A.Wilson, S.J.Davis.

ABSTRACT

Native and non-native ligands of the T cell receptor (TCR), including antibodies, have been proposed to induce signaling in T cells via intra- or intersubunit conformational rearrangements within the extracellular regions of TCR complexes. We have investigated whether any signatures can be found for such postulated structural changes during TCR triggering induced by antibodies, using crystallographic and mutagenesis-based approaches. The crystal structure of murine CD3ε complexed with the mitogenic anti-CD3ε antibody 2C11 enabled the first direct structural comparisons of antibody-liganded and unliganded forms of CD3ε from a single species, which revealed that antibody binding does not induce any substantial rearrangements within CD3ε. Saturation mutagenesis of surface-exposed CD3ε residues, coupled with assays of antibody-induced signaling by the mutated complexes, suggests a new configuration for the complex within which CD3ε is highly exposed and reveals that no large new CD3ε interfaces are required to form during antibody-induced signaling. The TCR complex therefore appears to be a structure that is capable of initiating intracellular signaling in T cells without substantial structural rearrangements within or between the component subunits. Our findings raise the possibility that signaling by native ligands might also be initiated in the absence of large structural rearrangements in the receptor.