Structural Model of the Extracellular Assembly of the TCR-CD3 Complex

• DOI: 10.1016/j.celrep.2016.02.081
• Publication Date: 2016-03-17T19:06:06Z
• Authors: Aswin Natarajan; Vidushan Nadarajah; Klara Felsovalyi; Wenjuan Wang; Vivian R. Jeyacha...; Riley A. Wasson; Timothy Cardozo; Clay Bracken; Michelle Krogsgaard
• Keywords: Models, Molecular; 0303 health sciences; CD3 Complex; QH301-705.5; Receptors, Antigen, T-Cell; Protein Structure, Secondary; Protein Structure, Tertiary; 03 medical and health sciences; Receptor-CD3 Complex, Antigen, T-Cell; Mutagenesis, Site-Directed; Humans; Protein Interaction Domains and Motifs; Biology (General); Nuclear Magnetic Resonance, Biomolecular

Highlights•CD3γε and CD3δε can individually bind to the TCR yield a two-sided binding model•CD3γε binds β subunit α subunit•The molecular basis of TCR-CD3 interactions is examined through NMR spectroscopy•The extracellular structure revealed using computational dockingSummaryAntigen recognition peptide-major histocompatibility complexes (pMHCs) by T cells, key step in initiating adaptive immune responses, performed cell receptor (TCR) bound CD3 heterodimers. However, biophysical transmission interaction into productive intracellular signaling sequence remains incomplete. Here we used nuclear magnetic resonance (NMR) spectroscopy combined with mutational analysis docking derive structural model assembly. In inactivated state, CD3γε interacts helix 3 4-F strand regions Cβ subunit, whereas F C Cα this model, placing subunits on opposing sides TCR. This work identifies contacts between subunits, identifying physical for transmitting an activating signal complex.Graphical abstract