2hac | pdb_00002hac
Structure of Zeta-Zeta Transmembrane Dimer
Structural highlights
Disease[CD3Z_HUMAN] Defects in CD247 are the cause of immunodeficiency due to defect in CD3-zeta (CD3ZID) [MIM:610163]. An immunological deficiency characterized by T-cells impaired immune response to alloantigens, tetanus toxoid and mitogens.[1] Function[CD3Z_HUMAN] Probable role in assembly and expression of the TCR complex as well as signal transduction upon antigen triggering. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe T cell receptor (TCR) alphabeta heterodimer communicates ligand binding to the cell interior via noncovalently associated CD3gammaepsilon, CD3deltaepsilon, and zetazeta dimers. While structures of extracellular components of the TCR-CD3 complex are known, the transmembrane (TM) domains that mediate assembly have eluded structural characterization. Incorporation of the zetazeta signaling module is known to require one basic TCRalpha and two zetazeta aspartic acid TM residues. We report the NMR structure of the zetazeta(TM) dimer, a left-handed coiled coil with substantial polar contacts. Mutagenesis experiments demonstrate that three polar positions are critical for zetazeta dimerization and assembly with TCR. The two aspartic acids create a single structural unit at the zetazeta interface stabilized by extensive hydrogen bonding, and there is evidence for a structural water molecule (or molecules) within close proximity. This structural unit, representing only the second transmembrane dimer interface solved to date, serves as a paradigm for the assembly of all modules involved in TCR signaling. The structure of the zetazeta transmembrane dimer reveals features essential for its assembly with the T cell receptor.,Call ME, Schnell JR, Xu C, Lutz RA, Chou JJ, Wucherpfennig KW Cell. 2006 Oct 20;127(2):355-68. PMID:17055436[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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