2JXB

Structure of CD3epsilon-Nck2 first SH3 domain complex

Summary for 2JXB

• Entry DOI: 10.2210/pdb2jxb/pdb
• Descriptor: T-cell surface glycoprotein CD3 epsilon chain, Cytoplasmic protein NCK2 (1 entity in total)
• Functional Keywords: nck, cd3epsilon, t-cell receptor, sh3 domain, immunology, cytoplasm, sh2 domain, signaling protein complex
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P07766
• Total number of polymer chains: 1
• Total formula weight: 10267.66

Authors

Takeuchi, K.,Yang, H.,Ng, E.,Park, S.,Sun, Z.J.,Reinherz, E.L.,Wagner, G. (deposition date: 2007-11-09, release date: 2008-09-23, Last modification date: 2024-05-29)

Primary citation

Takeuchi, K.,Yang, H.,Ng, E.,Park, S.Y.,Sun, Z.Y.,Reinherz, E.L.,Wagner, G.
Structural and functional evidence that Nck interaction with CD3epsilon regulates T-cell receptor activity.
J.Mol.Biol., 380:704-716, 2008

PubMed Abstract: Recruitment of signaling molecules to the cytoplasmic domains of the CD3 subunits of the T-cell receptor (TCR) is crucial for early T-cell activation. These transient associations either do or do not require tyrosine phosphorylation of CD3 immune tyrosine activation motifs (ITAMs). Here we show that the non-ITAM-requiring adaptor protein Nck forms a complex with an atypical PxxDY motif of the CD3epsilon tail, which encompasses Tyr166 within the ITAM and a TCR endocytosis signal. As suggested by the structure of the complex, we find that Nck binding inhibits phosphorylation of the CD3epsilon ITAM by Fyn and Lck kinases in vitro. Moreover, the CD3epsilon-Nck interaction downregulates TCR surface expression upon physiological stimulation in mouse primary lymph node cells. This indicates that Nck performs an important regulatory function in T lymphocytes by inhibiting ITAM phosphorylation and/or removing cell surface TCR via CD3epsilon interaction.

PubMed: 18555270
DOI: 10.1016/j.jmb.2008.05.037

Experimental method

SOLUTION NMR