scholarly journals The Intrinsically Disordered Cytoplasmic Domain of the T Cell Receptor ζ Chain Binds to the Nef Protein of Simian Immunodeficiency Virus without a Disorder-to-Order Transition†

Biochemistry ◽  
2008 ◽  
Vol 47 (49) ◽  
pp. 12942-12944 ◽  
Author(s):  
Alexander B. Sigalov ◽  
Walter M. Kim ◽  
Maria Saline ◽  
Lawrence J. Stern
Keyword(s):  
T Cell ◽  
Simian Immunodeficiency Virus ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Cytoplasmic Domain ◽  
Order Transition ◽  
Intrinsically Disordered ◽  
Immunodeficiency Virus

scholarly journals Cooperative Interactions of Simian Immunodeficiency Virus Nef, AP-2, and CD3-ζ Mediate the Selective Induction of T-Cell Receptor-CD3 Endocytosis

2003 ◽  
Vol 77 (14) ◽  
pp. 8116-8126 ◽  
Author(s):  
Tomek Swigut ◽  
Michael Greenberg ◽  
Jacek Skowronski
Keyword(s):  
T Cell ◽  
Simian Immunodeficiency Virus ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Cytoplasmic Domain ◽  
Membrane Receptors ◽  
Binding Studies ◽  
Vitro Binding ◽  
Immunodeficiency Virus

ABSTRACT The Nef proteins of human immunodeficiency virus and simian immunodeficiency virus (SIV) bind the AP-1 and AP-2 clathrin adaptors to downmodulate the expression of CD4 and CD28 by recruiting them to sites of AP-2 clathrin-dependent endocytosis. Additionally, SIV Nef directly binds the CD3-ζ subunit of the CD3 complex and downmodulates the T-cell receptor (TCR)-CD3 complex. We report here that SIV mac239 Nef induces the endocytosis of TCR-CD3 in Jurkat T cells. SIV Nef also induces the endocytosis of a chimeric CD8-CD3-ζ protein containing only the CD3-ζ cytoplasmic domain (8-ζ), in the absence of other CD3 subunits. Thus, the interaction of SIV Nef with CD3-ζ likely mediates the induction of TCR-CD3 endocytosis. In cells expressing SIV Nef and 8-ζ, both proteins colocalize with AP-2, indicating that Nef induces 8-ζ internalization via this pathway. Surprisingly, deletion of constitutively strong AP-2 binding determinants (CAIDs) in SIV Nef had little effect on its ability to induce TCR-CD3, or 8-ζ endocytosis, even though these determinants are required for the induction of CD4 and CD28 endocytosis via this pathway. Fluorescent microscopic analyses revealed that while neither the mutant SIV Nef protein nor 8-ζ colocalized with AP-2 when expressed independently, both proteins colocalized with AP-2 when coexpressed. In vitro binding studies using recombinant SIV Nef proteins lacking CAIDs and recombinant CD3-ζ cytoplasmic domain demonstrated that SIV Nef and CD3-ζ cooperate to bind AP-2 via a novel interaction. The fact that Nef uses distinct AP-2 interaction surfaces to recruit specific membrane receptors demonstrates how Nef independently selects distinct types of target receptors and recruits them to AP-2 for endocytosis.

scholarly journals The T-Cell Receptor ζ Chain Contains Two Homologous Domains with Which Simian Immunodeficiency Virus Nef Interacts and Mediates Down-Modulation

2000 ◽  
Vol 74 (7) ◽  
pp. 3273-3283 ◽  
Author(s):  
Todd M Schaefer ◽  
Ian Bell ◽  
Beth A. Fallert ◽  
Todd A. Reinhart
Keyword(s):  
T Cell ◽  
Simian Immunodeficiency Virus ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Cytoplasmic Domain ◽  
Thymocyte Development ◽  
Interaction Domain ◽  
Immunodeficiency Virus ◽  
Specific Factors ◽  
Two Hybrid

ABSTRACT We have recently demonstrated that simian immunodeficiency virus (SIV) Nef binds to the ζ chain of the T-cell receptor (TCR), leading to its down-modulation from T-cell surfaces (I. Bell, C. Ashman, J. Maughan, E. Hooker, F. Cook, and T. A. Reinhart, J. Gen. Virol. 79:2717–2727, 1998). Using a panel of human as well as rhesus macaque TCR ζ cytoplasmic domain mutants, we have identified in this report two linear peptides in the cytoplasmic domain of TCR ζ which independently interact with SIV Nef. Each SIV Nef interaction domain was sufficient in the absence of the other for interaction with SIV Nef in a yeast two-hybrid assay. In parallel, we demonstrated that Nef down-modulation of CD8-TCR ζ fusion proteins containing full-length or truncated portions of the TCR ζ cytoplasmic domain occurs in transiently transfected 293T cells. Furthermore, using proteins expressed in Escherichia coli, a glutathioneS-transferase–Nef fusion protein coprecipitated histidine-tagged portions of the TCR ζ cytoplasmic domain which contained SNID-1 or SNID-2. The peptides targeted by SIV Nef, YNELNL and YSEIGMKGERRR, are portions of the first and second of three immunoreceptor tyrosine-based activation motifs which are important in signal transduction, thymocyte development, and TCR biogenesis. These results demonstrate that SIV Nef binds to two distinct domains on TCR ζ in the absence of other T-cell-specific factors, and that interaction with either domain is sufficient to cause down-modulation of TCR ζ.

scholarly journals T cell receptor-dependent cell death of T cell hybridomas mediated by the CD30 cytoplasmic domain in association with tumor necrosis factor receptor-associated factors.

1996 ◽  
Vol 183 (2) ◽  
pp. 669-674 ◽  
Author(s):  
S Y Lee ◽  
C G Park ◽  
Y Choi
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
T Cell Receptor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Cell Receptor ◽  
Cytoplasmic Domain ◽  
Activated T Cells ◽  
Necrosis Factor

CD30 is a member of the tumor necrosis factor superfamily and a surface marker for Hodgkin's disease. Normal activated T cells and several virally transformed T or B cell lines also show CD30 expression. The interaction of CD30 with its ligand induces cell death or proliferation, depending on the cell type. In this report we characterize the signals mediated by the intracellular domain of CD30 and show that, in combination with signal(s) transduced by the T cell receptor, the multimerization of CD30 cytoplasmic domain induces Fas(CD95)-independent cell death in T cell hybridomas. Deletion analysis shows that the COOH-terminal 66 amino acids of CD30 are required to induce cell death. Using the yeast two-hybrid system, we have identified that the same region of CD30 interacts with tumor necrosis factor receptor-associated factor (TRAF)1 and TRAF2. These results indicate that TRAF1 and/or TRAF2 play an important role in cell death in addition to their previously identified roles in cell proliferation.

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