Structural characterization of the TCR complex by electron microscopy

TY - JOUR

T1 - Structural characterization of the TCR complex by electron microscopy

AU - Arechaga, Ignacio

AU - Swamy, Mahima

AU - Abia, David

AU - Schamel, Wolfgang A.

AU - Alarcón, Balbino

AU - Valpuesta, José María

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Structural information on how the TCR transmits signals upon binding of its antigen peptide MHC molecule ligand is still lacking. The ectodomains of the TCRα/β, CD3∈γ and CD3∈δ dimers, as well as the transmembrane domain of CD3ζ, have been characterized by X-ray crystallography and nuclear magnetic resonance (NMR). However, no structural data have been obtained for the entire TCR complex. In this study, we have purified the TCR from T cells under native conditions and used electron microscopy to derive a three-dimensional structure. The TCR complex appears as a pear-shaped structure of 180 × 120 × 65 Å Furthermore, the use of mAbs has allowed to determine the orientation of the TCRα/β and CD3 subunits and to suggest a model of interactions. Interestingly, the reconstructed TCR is larger than expected for a complex with a αβγ∈δ∈ζζ stoichiometry. The accommodation of a second TCRαβ to fill in the extra volume is discussed.

AB - Structural information on how the TCR transmits signals upon binding of its antigen peptide MHC molecule ligand is still lacking. The ectodomains of the TCRα/β, CD3∈γ and CD3∈δ dimers, as well as the transmembrane domain of CD3ζ, have been characterized by X-ray crystallography and nuclear magnetic resonance (NMR). However, no structural data have been obtained for the entire TCR complex. In this study, we have purified the TCR from T cells under native conditions and used electron microscopy to derive a three-dimensional structure. The TCR complex appears as a pear-shaped structure of 180 × 120 × 65 Å Furthermore, the use of mAbs has allowed to determine the orientation of the TCRα/β and CD3 subunits and to suggest a model of interactions. Interestingly, the reconstructed TCR is larger than expected for a complex with a αβγ∈δ∈ζζ stoichiometry. The accommodation of a second TCRαβ to fill in the extra volume is discussed.

KW - CD3

KW - Purification

KW - Structure

KW - TCR

UR - https://www.scopus.com/pages/publications/78649799809

U2 - 10.1093/intimm/dxq443

DO - 10.1093/intimm/dxq443

M3 - Article

C2 - 21059766

AN - SCOPUS:78649799809

SN - 0953-8178

VL - 22

SP - 897

EP - 903

JO - International Immunology

JF - International Immunology

IS - 11

ER -