Abstract
Prostatic acid phosphatase (PAP) assembles into amyloid fibrils that facilitate infection by HIV. Its peptide fragments PAP(248–286) and PAP(85–120) also enhance attachment of the virus by viral adhesion to the host cell prior to receptor-specific binding via reducing the electrostatic repulsion between the membranes of the virus and the target cell. The secondary structure of monomeric PAP(248–286) in a biomembrane-mimicking environment can be separated into an N-terminal unordered region, an α-helical central domain, and an α/310-helical C-terminal section (Nanga et al., J. Am. Chem. Soc., 131:17972–17979, 2009). In this work, we used two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy techniques to study spatial structures of isolated central [PAP(262–270)] and C-terminal [PAP(274–284)] fragments of PAP(248–286) in SDS micelle solutions. NMR studies revealed the formation of complexes of both peptides with SDS micelles, with attraction to the micelle membranes occurring mainly through nonpolar and uncharged residues of the peptides. We demonstrate that, when interacting with SDS micelles, PAP(262–270) and PAP(274–284) form α-helical and 310-helical secondary structures, respectively, similar to that found previously for the 39-residue PAP(248–286).
Similar content being viewed by others
References
D.S. Dimitrov, R.L. Willey, H. Sato, L.J. Chang, R. Blumenthal, M.A. Martin, Virology 67, 2182–2190 (1993)
J. Munch, E. Rucker, L. Standker, K. Adermann, C. Goffinet, M. Schindler, S. Wildum, R. Chinnadurai, D. Rajan, A. Specht, G. Gimenez-Gallego, P.C. Sanchez, D.M. Fowler, A. Koulov, J.W. Kelly, W. Mothes, J.C. Grivel, L. Margolis, O.T. Keppler, W.G. Forssmann, F. Kirchhoff, Cell 131, 1059–1071 (2007)
F. Arnold, J. Schnell, O. Zirafi, C. Sturzel, C. Meier, T. Well, L. Standker, W.-G. Forssmann, N.R. Roan, W.C. Greene, F. Kirchhoff, J. Munch, J. Virol. 86, 1244–1249 (2012)
N.R. Roan, J. Münch, N. Arhel, W. Mothes, J. Neidleman, A. Kobayashi, K. Smith-McCune, F. Kirchhoff, W.C. Greene, J. Virol. 83, 73–80 (2009)
N.R. Roan, S. Sowinski, J. Munch, F. Kirchhoff, W.C. Greene, J. Biol. Chem. 285, 1861–1869 (2010)
J.R. Brender, R.P. Nanga, N. Popovych, R. Soong, P.M. Macdonald, A. Ramamoorthy, Biochim. Biophys. Acta 1808, 1161–1169 (2011)
R.P.R. Nanga, J.R. Brender, S. Vivekanandan, N. Popovych, A. Ramamoorthy, J. Am. Chem. Soc. 131, 17972–17979 (2009)
D.S. Blochin, O.V. Aganova, A.R. Yulmetov, A.V. Filippov, B.I. Gizatullin, S. Afonin, O.N. Antzutkin, V.V. Klochkov, J. Mol. Struct. 1033, 59–66 (2013)
D.S. Blokhin, A.V. Filippov, O.N. Antzutkin, FKh Karataeva, V.V. Klochkov, J. Mol. Struct. 1070, 38–42 (2014)
A.V. Filippov, A. Khakimov, S. Afonin, O.N. Antzutkin, Mendeleev Commun. 23, 313–315 (2013)
J.R. Brender, K. Hartman, L.M. Gottler, E.C. Cavitt, D.W. Youngstrom, A. Ramamoorthy, Biophys. J. 97, 2474–2483 (2009)
S. Berger, S. Braun, 200 and More NMR Experiments (Wiley-VCH, Weinheim, 2004)
G.S. Rule, T.K. Hitchens, Fundamentals of Protein NMR Spectroscopy (Springer, Berlin, 2006)
C.D. Schwieters, J.J. Kuszewski, N. Tjandra, G.M. Clore, J. Magn. Reson. 160, 65–73 (2003)
W. Braun, G. Wider, K.H. Lee, K. Wüthrich, J. Mol. Biol. 169, 921–948 (1983)
A. Motta, A. Pastore, N.A. Goud, M.A. Castiglione-Morelli, Biochemistry 30, 10444–10450 (1991)
G. Wang, P. Keifer, A. Peterkofsky, Protein Sci. 12, 1087–1096 (2003)
D.S. Blokhin, S.V. Efimov, A.V. Klochkov, A.R. Yulmetov, A.V. Filippov, O.N. Antzutkin, A.V. Aganov, V.V. Klochkov, Appl. Magn. Reson. 41, 267–282 (2011)
D.S. Blokhin, S. Berger, V.V. Klochkov, Magn. Reson. Solids 15(2), 13202–13209 (2013)
K.S. Usachev, A.V. Filippov, B.I. Khairutdinov, O.N. Antzutkin, V.V. Klochkov, J. Mol. Struct. 1076, 518–523 (2014)
D.S. Wishart, B.D. Sykes, F.M. Richards, Biochemistry 31, 1647–1651 (1992)
Acknowledgments
Financial support from the Russian Foundation for Basic Research (Project No. 12-04-00011-a and Project No. 13-03-97041 r-povolzh’e-a) and the Ministry of Education and Science of the Russian Federation (Contract No. 02.740.11.0702) is gratefully acknowledged. This work was also funded by a subsidy from the Russian government to support the Program of Competitive Growth of Kazan Federal University among the World’s Leading Academic Centers. We thank the Foundation in Memory of J.C. and Seth M. Kempe (Grant Nos. JCK-2701 and JCK-2905, used to purchase a peptide synthesizer, HPLC, and chemicals).
Author information
Authors and Affiliations
Corresponding author
Additional information
Structural data are available in the Protein Data Bank/BioMagResBank databases under the accession numbers 2MG0/19580 and 2MIR/19690.
Rights and permissions
About this article
Cite this article
Blokhin, D.S., Filippov, A.V., Antzutkin, O.N. et al. Spatial Structures of PAP(262–270) and PAP(274–284), Two Selected Fragments of PAP(248–286), an Enhancer of HIV Infectivity. Appl Magn Reson 46, 757–769 (2015). https://doi.org/10.1007/s00723-015-0669-0
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00723-015-0669-0