Endocytic sorting motif interactions involved in Nef-mediated downmodulation of CD4 and

Nature Communications

Volumn 8, Issue 1, 2017, Pages

  Manrique, Santiago ^a,b   Sauter, Daniel ^c   Horenkamp, Florian A ^b   Lülf, Sebastian ^b,d   Yu, Hangxing ^c   Hotter, Dominik ^c   Anand, Kanchan ^a,d   Kirchhoff, Frank ^c   Geyer, Matthias ^a,b,d  

^a UNIVERSITY OF BONN   (Germany)

^b MAX PLANCK INSTITUTE OF MOLECULAR PHYSIOLOGY   (Germany)

^c UNIVERSITY HOSPITAL ULM   (Germany)

^d CENTER OF ADVANCED EUROPEAN STUDIES AND RESEARCH CAESAR   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CD3 ANTIGEN; CD4 ANTIGEN; NEF PROTEIN; TYROSINE; CELL SURFACE RECEPTOR; MUTANT PROTEIN; PROTEIN BINDING; TRANSCRIPTION FACTOR AP 2;

CELLS AND CELL COMPONENTS; FUNCTIONAL ROLE; GENETIC ANALYSIS; HUMAN IMMUNODEFICIENCY VIRUS; MOLECULAR ANALYSIS; PATHOGENICITY; PEPTIDE; VIRUS;

ARTICLE; CELL SELECTION; CRYSTAL STRUCTURE; DOWN REGULATION; ENDOSOME; GAIN OF FUNCTION MUTATION; HYDROPHOBICITY; INTERNALIZATION; MOLECULAR INTERACTION; NONHUMAN; PROTEIN BINDING; PROTEIN INTERACTION; PROTEIN MOTIF; SIMIAN IMMUNODEFICIENCY VIRUS; CHEMISTRY; ENDOCYTOSIS; GENETICS; HEK293 CELL LINE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; METABOLISM; MOLECULAR MODEL; MONONUCLEAR CELL; MUTATION; X RAY CRYSTALLOGRAPHY;

HUMAN IMMUNODEFICIENCY VIRUS 1; SIMIAN IMMUNODEFICIENCY VIRUS;

AMINO ACID MOTIFS; CD3 COMPLEX; CD4 ANTIGENS; CRYSTALLOGRAPHY, X-RAY; DOWN-REGULATION; ENDOCYTOSIS; GENE PRODUCTS, NEF; HEK293 CELLS; HIV-1; HUMANS; LEUKOCYTES, MONONUCLEAR; MODELS, MOLECULAR; MUTANT PROTEINS; MUTATION; PROTEIN BINDING; RECEPTORS, CELL SURFACE; SIMIAN IMMUNODEFICIENCY VIRUS; TRANSCRIPTION FACTOR AP-2;

EID: 85028877835     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/s41467-017-00481-z     Document Type: Article

References (62)

1. Deacon, N. J. et al. Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Science 270, 988-991 (1995)
2. Kirchhoff, F., Greenough, T. C., Brettler, D. B., Sullivan, J. L. & Desrosiers, R. C. Brief report: absence of intact nef sequences in a long-term survivor with nonprogressive HIV-1 infection. N. Engl. J. Med. 332, 228-332 (1995)
3. Rosa, A. et al. HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation. Nature 526, 212-217 (2015)
4. Usami, Y., Wu, Y. & Göttlinger, H. G. SERINC3 and SERINC5 restrict HIV-1 infectivity and are counteracted by Nef. Nature 526, 218-223 (2015)
5. Bell, I. et al. Association of simian immunodeficiency virus Nef with the T-cell receptor (TCR) zeta chain leads to TCR down-modulation. J. Gen. Virol. 79, 2717-2727 (1998)
6. Guy, B. et al. HIV F/3′ orf encodes a phosphorylated GTP-binding protein resembling an oncogene product. Nature 330, 266-269 (1987)
7. Schwartz, O., Maréchal, V., Le Gall, S., Lemonnier, F. & Heard, J. M. Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nat. Med. 2, 338-342 (1996)
8. Benson, R. E., Sanfridson, A., Ottinger, J. S., Doyle, C. & Cullen, B. R. Downregulation of cell-surface CD4 expression by simian immunodeficiency virus Nef prevents viral super infection. J. Exp. Med. 177, 1561-1566 (1993)
9. Aiken, C., Konner, J., Landau, N. R., Lenburg, M. E. & Trono, D. Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain. Cell 76, 853-864 (1994)
10. Wildum, S., Schindler, M., Münch, J. & Kirchhoff, F. Contribution of Vpu, Env, and Nef to CD4 down-modulation and resistance of human immunodeficiency virus type 1-infected T cells to superinfection. J. Virol. 80, 8047-8059 (2006)
11. Schindler, M. et al. Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1. Cell 125, 1055-1067 (2006)
12. Arhel, N. et al. The inability to disrupt the immunological synapse between infected human T cells and APCs distinguishes HIV-1 from most other primate lentiviruses. J. Clin. Invest. 119, 2965-2975 (2009)
13. Fenard, D. et al. Nef is physically recruited into the immunological synapse and potentiates T cell activation early after TCR engagement. J. Immunol. 175, 6050-6057 (2005)
14. Thoulouze, M. I. et al. Human immunodeficiency virus type-1 infection impairs the formation of the immunological synapse. Immunity 24, 547-561 (2006)
15. Abraham, L. & Fackler, O. T. HIV-1 Nef: a multifaceted modulator of T cell receptor signaling. Cell Commun. Signal 10, 39 (2012)
16. Kirchhoff, F. Immune evasion and counteraction of restriction factors by HIV-1 and other primate lentiviruses. Cell Host Microbe 8, 55-67 (2010)
17. Iafrate, A. J., Bronson, S. & Skowronski, J. Separable functions of Nef disrupt two aspects of T cell receptor machinery: CD4 expression and CD3 signaling. EMBO J. 16, 673-684 (1997)
18. Schaefer, T. M. et al. The conserved process of TCR/CD3 complex down-modulation by SIV Nef is mediated by the central core, not endocytic motifs. Virology 302, 106-122 (2002)
19. Greenberg, M. E. et al. Co-localization of HIV-1 Nef with the AP-2 adaptor protein complex correlates with Nef-induced CD4 down-regulation. EMBO J. 16, 6964-6976 (1997)
20. Bresnahan, P. A. et al. A dileucine motif in HIV-1 Nef acts as an internalization signal for CD4 downregulation and binds the AP-1 clathrin adaptor. Curr. Biol. 8, 1235-1238 (1998)
21. Kirchhausen, T., Owen, D. & Harrison, S. C. Molecular structure, function, and dynamics of clathrin-mediated membrane traffic. Cold Spring Harb. Perspect. Biol. 6, a016725 (2014)
22. Pitcher, C., Höning, S., Fingerhut, A., Bowers, K. & Marsh, M. Cluster of differentiation antigen 4 (CD4) endocytosis and adaptor complex binding require activation of the CD4 endocytosis signal by serine phosphorylation. Mol. Biol. Cell 10, 677-691 (1999)
23. Garcia, J. V. & Miller, A. D. Serine phosphorylation-independent downregulation of cell-surface CD4 by Nef. Nature 350, 508-511 (1991)
24. Osman, N., Lucas, S. & Cantrell, D. The role of tyrosine phosphorylation in the interaction of cellular tyrosine kinases with the T cell receptor zeta chain tyrosine-based activation motif. Eur. J. Immunol. 25, 2863-2869 (1995)
25. Schaefer, T. M., Bell, I., Fallert, B. A. & Reinhart, T. A. The T-cell receptor zeta chain contains two homologous domains with which simian immunodeficiency virus Nef interacts and mediates down-modulation. J. Virol. 74, 3273-3283 (2000)
26. Oldridge, J. & Marsh, M. Nef-an adaptor adaptor Trends Cell Biol. 8, 302-305 (1998)
27. Geyer, M., Fackler, O. T. & Peterlin, B. M. Structure-function relationships in HIV-1 Nef. EMBO Rep. 2, 580-585 (2001)
28. Lee, C. H., Saksela, K., Mirza, U. A., Chait, B. T. & Kuriyan, J. Crystal structure of the conserved core of HIV-1 Nef complexed with a Src family SH3 domain. Cell 85, 931-942 (1996)
29. Grzesiek, S., Stahl, S. J., Wingfield, P. T. & Bax, A. The CD4 determinant for downregulation by HIV-1 Nef directly binds to Nef. Mapping of the Nef binding surface by NMR. Biochemistry 35, 10256-10261 (1996)
30. Geyer, M., Munte, C. E., Schorr, J., Kellner, R. & Kalbitzer, H. R. Structure of the anchor-domain of myristoylated and non-myristoylated HIV-1 Nef protein. J. Mol. Biol. 289, 123-138 (1999)
31. Hiipakka, M. & Saksela, K. Capacity of simian immunodeficiency virus strain mac Nef for high-affinity Src homology 3 (SH3) binding revealed by ligand-tailored SH3 domains. J. Gen. Virol. 83, 3147-3152 (2002)
32. Sharp, P. M. & Hahn, B. H. Origins of HIV and the AIDS pandemic. Cold Spring Harb. Perspect. Med. 1, a006841 (2011)
33. Lülf, S. et al. Structural basis for the inhibition of HIV-1 Nef by a high-affinity binding single-domain antibody. Retrovirology 11, 24 (2014)
34. Breuer, S. et al. Biochemical indication for myristoylation-dependent conformational changes in HIV-1 Nef. Biochemistry 45, 2339-2349 (2006)
35. Kim, W. M., Sigalov, A. B. & Stern, L. J. Pseudo-merohedral twinning and noncrystallographic symmetry in orthorhombic crystals of SIVmac239 Nef core domain bound to different-length TCRzeta fragments. Acta Crystallogr. D Biol. Crystallogr. 66, 163-175 (2010)
36. Aiken, C., Krause, L., Chen, Y. L. & Trono, D. Mutational analysis of HIV-1 Nef: identification of two mutants that are temperature-sensitive for CD4 downregulation. Virology 217, 293-300 (1996)
37. Fackler, O. T. et al. Functional characterization of HIV-1 Nef mutants in the context of viral infection. Virology 351, 322-329 (2006)
38. Horenkamp, F. A. et al. Conformation of the dileucine-based sorting motif in HIV-1 Nef revealed by intermolecular domain assembly. Traffic 12, 867-877 (2011)
39. Lülf, S., Horenkamp, F. A., Breuer, S. & Geyer, M. Nef surfaces: where to interfere with function. Curr. HIV Res. 9, 543-551 (2011)
40. Hrecka, K., Swigut, T., Schindler, M., Kirchhoff, F. & Skowronski, J. Nef proteins from diverse groups of primate lentiviruses downmodulate CXCR4 to inhibit migration to the chemokine stromal derived factor 1. J. Virol. 79, 10650-10659 (2005)
41. Swigut, T., Greenberg, M. & Skowronski, J. Cooperative interactions of simian immunodeficiency virus Nef, AP-2, and CD3-zeta mediate the selective induction of T-cell receptor-CD3 endocytosis. J. Virol. 77, 8116-8126 (2003)
42. Stumptner-Cuvelette, P. et al. HIV-1 Nef impairs MHC class II antigen presentation and surface expression. Proc. Natl. Acad. Sci. USA 98, 12144-12149 (2001)
43. Ren, X., Park, S. Y., Bonifacino, J. S. & Hurley, J. H. How HIV-1 Nef hijacks the AP2 clathrin adaptor to downregulate CD4. eLife 3, e01754 (2014)
44. Jackson, L. P. et al. A large-scale conformational change couples membrane recruitment to cargo binding in the AP2 clathrin adaptor complex. Cell 141, 1220-1229 (2010)
45. Collins, B. M., McCoy, A. J., Kent, H. M., Evans, P. R. & Owen, D. J. Molecular architecture and functional model of the endocytic AP2 complex. Cell 109, 523-535 (2002)
46. Wu, H., Kwong, P. D. & Hendrickson, W. A. Dimeric association and segmental variability in the structure of human CD4. Nature 387, 527-530 (1997)
47. Wittlich, M., Thiagarajan, P., Koenig, B. W., Hartmann, R. & Willbold, D. NMR structure of the transmembrane and cytoplasmic domains of human CD4 in micelles. Biochim. Biophys. Acta 1798, 122-127 (2010)
48. Gondim, M. V. et al. AP-2 is the crucial clathrin adaptor protein for CD4 downmodulation by HIV-1 Nef in infected primary CD4+ T cells. J. Virol. 89, 12518-12524 (2015)
49. Poe, J. A. & Smithgall, T. E. HIV-1 Nef dimerization is required for Nef-mediated receptor downregulation and viral replication. J. Mol. Biol. 394, 329-342 (2009)
50. Giese, S. I. et al. Specific and distinct determinants mediate membrane binding and lipid raft incorporation of HIV-1(SF2) Nef. Virology 355, 175-191 (2006)
51. Gerlach, H. et al. HIV-1 Nef membrane association depends on charge, curvature, composition and sequence. Nat. Chem. Biol. 6, 46-53 (2010)
52. Akgun, B. et al. Conformational transition of membrane-associated terminally acylated HIV-1 Nef. Structure 21, 1822-1833 (2013)
53. Kabsch, W. XDS. Acta Cryst. D66, 125-132 (2010)
54. McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658-674 (2007)
55. Adams, P. D. et al. PHENIX: a comprehensive python-based system for macromolecular structure solution. Acta Cryst. D66, 213-221 (2010)
56. Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Cryst. D66, 486-501 (2010)
57. Winn, M. D. et al. Overview of the CCP4 suite and current developments. Acta Cryst. D67, 235-242 (2011)
58. Murshudov, G. N. et al. REFMAC5 for the refinement of macromolecular crystal structures. Acta Cryst. D67, 355-367 (2011)
59. Baker, N. A., Sept, D., Joseph, S., Holst, M. J. & McCammon, J. A. Electrostatics of nanosystems: application to microtubules and the ribosome. Proc. Natl. Acad. Sci. USA 98, 10037-10041 (2001)
60. Sauter, D. et al. Tetherin-driven adaptation of Vpu and Nef function and the evolution of pandemic and nonpandemic HIV-1 strains. Cell Host Microbe 6, 409-421 (2009)
61. Schmökel, J. et al. The presence of a vpu gene and the lack of Nef-mediated downmodulation of T cell receptor-CD3 are not always linked in primate lentiviruses. J. Virol. 85, 742-752 (2011)
62. Brenner, M. et al. Importance of the N-distal AP-2 binding element in Nef for simian immunodeficiency virus replication and pathogenicity in rhesus macaques. J. Virol. 80, 4469-4481 (2006).