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Solution structure of the human CD4 (403–419) receptor peptide

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Abstract

The cytoplasmic part of CD4 is known to be essential for the interaction with the human immunodeficiency virus type 1 proteins Vpu and Nef. The 17 amino acid synthetic peptide CD4 (403–419) with the amino acid sequence of the membrane proximal part of the cytoplasmic domain of the human CD4 receptor was structurally investigated by circular dichroism and nuclear magnetic resonance spectroscopy. The average α-helical content of the peptide could be estimated to be around 25%. Chemical shift index analysis and the connectivity pattern in nuclear Overhauser enhancement spectra located the α-helical part of the peptide from Gln403 to Arg412. It may be speculated that this amphipathic α-helix is the contact region with the Vpu and Nef proteins.

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References

  1. 1

    Bodenhausen G, Kogler H, Ernst RR. Selection of coherence-transfer pathways in NMR pulse experiments. J Magn Reson 58:370–388;1984.

  2. 2

    Bour S, Geleziunas R, Wainberg MA. The human immunodeficiency virus type 1 (HIV-1) CD4 receptor and its central role in promotion of HIV-1 infection. Microbiol Rev 59:63–93;1995.

  3. 3

    Brady RL, Dodson EJ, Dodson GG, Lange G, Davis SJ, Williams AF, Barclay AN. Crystal structure of domains 3 and 4 of rat CD4: Relation to the NH2-terminal domains. Science 260:979–983;1993.

  4. 4

    Brünger A. X-PLOR 3.1 Manual. New Haven, Yale University Press, 1993.

  5. 5

    Calnan BJ, Tidor S, Biancalana S, Hudson D, Frankel AD. Arginine-mediated RNA recognition: The arginine fork. Science 252:1167–1171;1991.

  6. 6

    Chen MY, Maldarelli F, Karczewski MK, Willey RL, Strebel K. Human immunodeficiency virus type 1 Vpu protein induces degradation of CD4 in vitro: The cytoplasmic domain of CD4 contributes to Vpu sensitivity. J Virol 67:3877–3884;1993.

  7. 7

    Creighton TE. Proteins: Structures and Molecular Properties. New York, Freeman, 1984.

  8. 8

    Dietrich J, Hou X, Wegener A-MK, Geisler C. CD3g contains a phosphoserine-dependent dileucine motif involved in down-regulation of the T cell receptor. EMBO J 13:2156–2166;1994.

  9. 9

    Englander SW, Wand AJ. Main-chain-directed strategy for the assignment of1H NMR spectra of proteins. Biochemistry 26:5953–5958;1987.

  10. 10

    Fesik SW, Zuiderweg ERP. Heteronuclear three-dimensional NMR spectroscopy: A strategy for the simplification of homonuclear two-dimensional NMR spectra. J Magn Reson 78:588–593;1988.

  11. 11

    Garrett TPJ, Wang J, Yan Y, Liu J, Harrison SC. Refinement and analysis of the structure of the first two domains of human CD4. J Mol Biol 234:763–778;1993.

  12. 12

    Griesinger C, Otting G, Wüthrich K, Ernst RR. Clean TOCSY for1H spin system identification in macromolecules. J Am Chem Soc 110:7870–7872;1988.

  13. 13

    Herrmann F. Thesis. University of Bayreuth, 1994.

  14. 14

    Higgins DG, Bleasby AJ, Fuchs R. CLUSTAL V: Improved software for multiple sequence alignments. Comput Appl Biosci 8:189–191;1992.

  15. 15

    Hunziker W, Fumey C. A di-leucine motif mediates endocytosis and basolateral sorting of macrophage IgG Fc receptors in MDCK cells. EMBO J 13:2963–2969;1994.

  16. 16

    Kabsch W, Sander C. Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22:2577–2637;1983.

  17. 17

    Letourneur F, Klausner RD. A novel di-leucine motif and a tyrosine based motif independently mediate lysosomal targeting and endocytosis of CD4 chains. Cell 69:1143–1157;1992.

  18. 18

    Marion D, Wüthrich K. Application of phase sensitive two-dimensional correlated spectroscopy (COSY) for measurements of1H-1H spin-spin coupling constants in proteins. Biochem Biophys Res Commun 113:967–974;1983.

  19. 19

    Pardi A, Billeter M, Wüthrich K. Calibration of the angular dependence of the amide proton-Cα proton coupling constants,3JHNα, in a globular protein. J Mol Biol 180:741–751;1984.

  20. 20

    Gibbs JS, Desrosiers RD. In: Cullen BR, ed. Human Retroviruses: Frontiers in Molecular Biology. Oxford, Oxford University Press, 137–158;1993.

  21. 21

    Rance M, Sørensen OW, Bodenhausen G, Wagner G, Ernst RR, Wüthrich K. Improved spectral resolution of COSY1H NMR spectra of proteins via double quantum filtering. Biochem Biophys Res Commun 117:479–485;1983.

  22. 22

    Salghetti S, Mariani R, Sokowronski J. Human immunodeficiency virus type 1 Nef and p56lck protein-tyrosine kinase interact with a common element in CD4 cytoplasmic tail. Proc Natl Acad Sci USA 92:349–353;1995.

  23. 23

    Schubert U, Henklein P, Boldyreff B, Wingender E, Strebel K, Porstmann T. The human immunodeficiency virus type 1 encoded Vpu protein is phosphorylated by casein kinase-2 (CK-2) at positions Ser52 and Ser56 within a predicted α-helix-turn α-helix-motif. J Mol Biol 236:16–25;1994.

  24. 24

    Schubert U, Strebel K. Differential activities of the human immunodeficiency virus type 1-encoded Vpu protein are regulated by phosphorylation and occur in different cellular compartments. J Virol 68:2260–2271;1994.

  25. 25

    Shin J, Dunbrack S, Lee S, Strominger JL. Phosphorylation dependent down-modulation of CD4 requires a specific structure within the cytoplasmic domain of CD4. J Biol Chem 266:10658–10665;1991.

  26. 26

    Willey RL, Maldarelli F, Martin MA, Strebel K. Human immunodeficiency virus type 1 Vpu protein induces rapid degradation of CD4. J Virol 66:7193–7200;1992.

  27. 27

    Wishart DS, Sykes BD, Richards FM. The chemical shift index: A fast and simple method for the assignment of protein secondary structure through NMR spectroscopy. Biochemistry 31:1647–1651;1992.

  28. 28

    Wray V, Federau T, Henklein P, Klabunde S, Kunert O, Schomburg D, Schubert U. Solution structure of the hydrophilic region of HVI-1 encoded virus protein U (Vpu) by CD and 1H NMR spectroscopy. Int J Pept Protein Res 45:35–43;1995.

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The authors thank Prof. F.X. Schmid for help with the CD spectra.

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Willbold, D., Rösch, P. Solution structure of the human CD4 (403–419) receptor peptide. J Biomed Sci 3, 435–441 (1996). https://doi.org/10.1007/BF02258047

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Key Words

  • CD4 (403–419) receptor peptide
  • Human immunodeficiency virus
  • Nuclear magnetic resonance spectroscopy
  • Structure, CD4 (403–419) receptor peptide
  • Vpu protein