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NMR solution structure of the 32-kDa platelet factor 4 ELR-motif N-terminal chimera: a symmetric tetramer.

Mayo KH, Roongta V, Ilyina E, Milius R, Barker S, Quinlan C, La Rosa G, Daly TJ
Biochemistry 34 11399-409 (1995)
Related entries: 1pfn, 1rhp

Cited: 29 times
EuropePMC logo PMID: 7547867

Abstract

Native human platelet factor 4 (PF4) is a homotetrameric protein (70 residues/subunit) known for its anticoagulant heparin binding activity. 2D 15N--1H HSQC NMR experiments of native PF4 in solution show the presence of conformational heterogeneity consistent with the formation of asymmetric homo-tetramers as observed in the X-ray crystal structure of both human and bovine PF4. A chimeric mutant of PF4 (called PF4-M2) which substitutes the first 11 N-terminal residues for the first eight residues from homologous interleukin-8 forms symmetric homo-tetramers with essentially the same heparin binding activity as native PF4. The solution structure of PF4-M2 has been investigated by using two- and three-dimensional 1H- and 15N-NMR spectroscopy and NOE-restrained simulated annealing molecular dynamics. As with other members of the CXC chemokine family whose structures are known, the PF4-M2 subunit monomer consists of a mostly hydrophobic, triple-stranded antiparallel beta-sheet onto which is folded an amphipathic C-terminal helix and a less periodic N-terminal domain. Although N-terminal substitution with the less acidic interleukin-8 sequence most affects the quarternary structure relative to native PF4 at the AC and AD dimer interfaces, AB dimer stability is weakened as reflected in reduced equilibrium association binding constants.

Reviews - 1pfm mentioned but not cited (2)

  1. Chemokines from a Structural Perspective. Miller MC, Mayo KH. Int J Mol Sci 18 (2017)
  2. Recent developments in vascular imaging techniques in tissue engineering and regenerative medicine. Upputuri PK, Sivasubramanian K, Mark CS, Pramanik M. Biomed Res Int 2015 783983 (2015)

Articles - 1pfm mentioned but not cited (3)

  1. CXC and CC chemokines form mixed heterodimers: association free energies from molecular dynamics simulations and experimental correlations. Nesmelova IV, Sham Y, Gao J, Mayo KH. J Biol Chem 283 24155-24166 (2008)
  2. Alternative C-terminal helix orientation alters chemokine function: structure of the anti-angiogenic chemokine, CXCL4L1. Kuo JH, Chen YP, Liu JS, Dubrac A, Quemener C, Prats H, Bikfalvi A, Wu WG, Sue SC. J Biol Chem 288 13522-13533 (2013)
  3. Chemokine CXCL7 Heterodimers: Structural Insights, CXCR2 Receptor Function, and Glycosaminoglycan Interactions. Brown AJ, Joseph PR, Sawant KV, Rajarathnam K. Int J Mol Sci 18 (2017)


Reviews citing this publication (6)

  1. Structure, function, and inhibition of chemokines. Fernandez EJ, Lolis E. Annu Rev Pharmacol Toxicol 42 469-499 (2002)
  2. Chemokine oligomerization in cell signaling and migration. Wang X, Sharp JS, Handel TM, Prestegard JH. Prog Mol Biol Transl Sci 117 531-578 (2013)
  3. Atomic features of an autoantigen in heparin-induced thrombocytopenia (HIT). Cai Z, Zhu Z, Greene MI, Cines DB. Autoimmun Rev 15 752-755 (2016)
  4. Heterodimers Are an Integral Component of Chemokine Signaling Repertoire. Kaffashi K, Dréau D, Nesmelova IV. Int J Mol Sci 24 11639 (2023)
  5. Heterologous Interactions with Galectins and Chemokines and Their Functional Consequences. Mayo KH. Int J Mol Sci 24 14083 (2023)
  6. The marriage of chemokines and galectins as functional heterodimers. von Hundelshausen P, Wichapong K, Gabius HJ, Mayo KH. Cell Mol Life Sci 78 8073-8095 (2021)

Articles citing this publication (18)

  1. Anginex, a designed peptide that inhibits angiogenesis. Griffioen AW, van der Schaft DW, Barendsz-Janson AF, Cox A, Struijker Boudier HA, Hillen HF, Mayo KH. Biochem J 354 233-242 (2001)
  2. Heparin is not required for detection of antibodies associated with heparin-induced thrombocytopenia/thrombosis. Visentin GP, Moghaddam M, Beery SE, McFarland JG, Aster RH. J Lab Clin Med 138 22-31 (2001)
  3. Platelet factor 4 and interleukin-8 CXC chemokine heterodimer formation modulates function at the quaternary structural level. Nesmelova IV, Sham Y, Dudek AZ, van Eijk LI, Wu G, Slungaard A, Mortari F, Griffioen AW, Mayo KH. J Biol Chem 280 4948-4958 (2005)
  4. Heparin binding to platelet factor-4. An NMR and site-directed mutagenesis study: arginine residues are crucial for binding. Mayo KH, Ilyina E, Roongta V, Dundas M, Joseph J, Lai CK, Maione T, Daly TJ. Biochem J 312 ( Pt 2) 357-365 (1995)
  5. A recipe for designing water-soluble, beta-sheet-forming peptides. Mayo KH, Ilyina E, Park H. Protein Sci 5 1301-1315 (1996)
  6. Atomic description of the immune complex involved in heparin-induced thrombocytopenia. Cai Z, Yarovoi SV, Zhu Z, Rauova L, Hayes V, Lebedeva T, Liu Q, Poncz M, Arepally G, Cines DB, Greene MI. Nat Commun 6 8277 (2015)
  7. Beta-sheet is the bioactive conformation of the anti-angiogenic anginex peptide. Dings RP, Arroyo MM, Lockwood NA, van Eijk LI, Haseman JR, Griffioen AW, Mayo KH. Biochem J 373 281-288 (2003)
  8. NMR analysis of the structure, dynamics, and unique oligomerization properties of the chemokine CCL27. Jansma AL, Kirkpatrick JP, Hsu AR, Handel TM, Nietlispach D. J Biol Chem 285 14424-14437 (2010)
  9. A surface plasmon resonance-based solution affinity assay for heparan sulfate-binding proteins. Cochran S, Li CP, Ferro V. Glycoconj J 26 577-587 (2009)
  10. The solution structure of the anti-HIV chemokine vMIP-II. Liwang AC, Wang ZX, Sun Y, Peiper SC, Liwang PJ. Protein Sci 8 2270-2280 (1999)
  11. NMR structure and dynamics of monomeric neutrophil-activating peptide 2. Young H, Roongta V, Daly TJ, Mayo KH. Biochem J 338 ( Pt 3) 591-598 (1999)
  12. Backbone and side-chain dynamics of residues in a partially folded beta-sheet peptide from platelet factor-4. Daragan VA, Ilyina EE, Fields CG, Fields GB, Mayo KH. Protein Sci 6 355-363 (1997)
  13. Measuring protein self-diffusion in protein-protein mixtures using a pulsed gradient spin-echo technique with WATERGATE and isotope filtering. Nesmelova IV, Idiyatullin D, Mayo KH. J Magn Reson 166 129-133 (2004)
  14. The anti-angiogenic peptide anginex disrupts the cell membrane. Pilch J, Franzin CM, Knowles LM, Ferrer FJ, Marassi FM, Ruoslahti E. J Mol Biol 356 876-885 (2006)
  15. NMR structure determination of the tetramerization domain of the Mnt repressor: An asymmetric alpha-helical assembly in slow exchange. Nooren IM, George AV, Kaptein R, Sauer RT, Boelens R. J Biomol NMR 15 39-53 (1999)
  16. Structural Evidence for the Tetrameric Assembly of Chemokine CCL11 and the Glycosaminoglycan Arixtra™. Dykstra AB, Sweeney MD, Leary JA. Biomolecules 3 905-922 (2013)
  17. A new obligate CXCL4-CXCL12 heterodimer for studying chemokine heterodimer activities and mechanisms. Nguyen KTP, Volkman B, Dréau D, Nesmelova IV. Sci Rep 12 17204 (2022)
  18. Deposition of macromolecular coordinates resulting from crystallographic and NMR studies. Wlodawer A. Nat Struct Biol 4 173-174 (1997)


Related citations provided by authors (1)

  1. Crystal structure of recombinant human platelet factor 4.. Zhang X, Chen L, Bancroft DP, Lai CK, Maione TE Biochemistry 33 8361-6 (1994)

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