| Structural highlights
Function
PPAP_HUMAN A non-specific tyrosine phosphatase that dephosphorylates a diverse number of substrates under acidic conditions (pH 4-6) including alkyl, aryl, and acyl orthophosphate monoesters and phosphorylated proteins. Has lipid phosphatase activity and inactivates lysophosphatidic acid in seminal plasma.[1] [2] [3] [4] Isoform 2: the cellular form also has ecto-5'-nucleotidase activity in dorsal root ganglion (DRG) neurons. Generates adenosine from AMP which acts as a pain suppressor. Acts as a tumor suppressor of prostate cancer through dephosphorylation of ERBB2 and deactivation of MAPK-mediated signaling.[5] [6] [7] [8]
Publication Abstract from PubMed
Semen is the main vector for HIV transmission worldwide. Recently, a peptide fragment (PAP(248-286)) has been isolated from seminal fluid that dramatically enhances HIV infectivity by up to 4-5 orders of magnitude. PAP(248-286) appears to enhance HIV infection by forming amyloid fibers known as SEVI, which are believed to enhance the attachment of the virus by bridging interactions between virion and host-cell membranes. We have solved the atomic-level resolution structure of the SEVI precursor PAP(248-286) using NMR spectroscopy in SDS micelles, which serve as a model membrane system. PAP(248-286), which does not disrupt membranes like most amyloid proteins, binds superficially to the surface of the micelle, in contrast to other membrane-disruptive amyloid peptides that generally penetrate into the core of the membrane. The structure of PAP(248-286) is unlike most amyloid peptides in that PAP(248-286) is mostly disordered when bound to the surface of the micelle, as opposed to the alpha-helical structures typically found of most amyloid proteins. The highly disordered nature of the SEVI peptide may explain the unique ability of SEVI amyloid fibers to enhance HIV infection as partially disordered amyloid fibers will have a greater capture radius for the virus than compact amyloid fibers. Two regions of nascent structure (an alpha-helix from V262-H270 and a dynamic alpha/3(10) helix from S279-L283) match the prediction of highly amyloidogenic sequences and may serve as nuclei for aggregation and amyloid fibril formation. The structure presented here can be used for the rational design of mutagenesis studies on SEVI amyloid formation and viral infection enhancement.
NMR structure in a membrane environment reveals putative amyloidogenic regions of the SEVI precursor peptide PAP(248-286).,Nanga RP, Brender JR, Vivekanandan S, Popovych N, Ramamoorthy A J Am Chem Soc. 2009 Dec 16;131(49):17972-9. PMID:19995078[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tanaka M, Kishi Y, Takanezawa Y, Kakehi Y, Aoki J, Arai H. Prostatic acid phosphatase degrades lysophosphatidic acid in seminal plasma. FEBS Lett. 2004 Jul 30;571(1-3):197-204. PMID:15280042 doi:10.1016/j.febslet.2004.06.083
- ↑ Munch J, Rucker E, Standker L, Adermann K, Goffinet C, Schindler M, Wildum S, Chinnadurai R, Rajan D, Specht A, Gimenez-Gallego G, Sanchez PC, Fowler DM, Koulov A, Kelly JW, Mothes W, Grivel JC, Margolis L, Keppler OT, Forssmann WG, Kirchhoff F. Semen-derived amyloid fibrils drastically enhance HIV infection. Cell. 2007 Dec 14;131(6):1059-71. PMID:18083097 doi:10.1016/j.cell.2007.10.014
- ↑ Hong S, Klein EA, Das Gupta J, Hanke K, Weight CJ, Nguyen C, Gaughan C, Kim KA, Bannert N, Kirchhoff F, Munch J, Silverman RH. Fibrils of prostatic acid phosphatase fragments boost infections with XMRV (xenotropic murine leukemia virus-related virus), a human retrovirus associated with prostate cancer. J Virol. 2009 Jul;83(14):6995-7003. doi: 10.1128/JVI.00268-09. Epub 2009 Apr 29. PMID:19403677 doi:10.1128/JVI.00268-09
- ↑ Chuang TD, Chen SJ, Lin FF, Veeramani S, Kumar S, Batra SK, Tu Y, Lin MF. Human prostatic acid phosphatase, an authentic tyrosine phosphatase, dephosphorylates ErbB-2 and regulates prostate cancer cell growth. J Biol Chem. 2010 Jul 30;285(31):23598-606. doi: 10.1074/jbc.M109.098301. Epub, 2010 May 24. PMID:20498373 doi:10.1074/jbc.M109.098301
- ↑ Tanaka M, Kishi Y, Takanezawa Y, Kakehi Y, Aoki J, Arai H. Prostatic acid phosphatase degrades lysophosphatidic acid in seminal plasma. FEBS Lett. 2004 Jul 30;571(1-3):197-204. PMID:15280042 doi:10.1016/j.febslet.2004.06.083
- ↑ Munch J, Rucker E, Standker L, Adermann K, Goffinet C, Schindler M, Wildum S, Chinnadurai R, Rajan D, Specht A, Gimenez-Gallego G, Sanchez PC, Fowler DM, Koulov A, Kelly JW, Mothes W, Grivel JC, Margolis L, Keppler OT, Forssmann WG, Kirchhoff F. Semen-derived amyloid fibrils drastically enhance HIV infection. Cell. 2007 Dec 14;131(6):1059-71. PMID:18083097 doi:10.1016/j.cell.2007.10.014
- ↑ Hong S, Klein EA, Das Gupta J, Hanke K, Weight CJ, Nguyen C, Gaughan C, Kim KA, Bannert N, Kirchhoff F, Munch J, Silverman RH. Fibrils of prostatic acid phosphatase fragments boost infections with XMRV (xenotropic murine leukemia virus-related virus), a human retrovirus associated with prostate cancer. J Virol. 2009 Jul;83(14):6995-7003. doi: 10.1128/JVI.00268-09. Epub 2009 Apr 29. PMID:19403677 doi:10.1128/JVI.00268-09
- ↑ Chuang TD, Chen SJ, Lin FF, Veeramani S, Kumar S, Batra SK, Tu Y, Lin MF. Human prostatic acid phosphatase, an authentic tyrosine phosphatase, dephosphorylates ErbB-2 and regulates prostate cancer cell growth. J Biol Chem. 2010 Jul 30;285(31):23598-606. doi: 10.1074/jbc.M109.098301. Epub, 2010 May 24. PMID:20498373 doi:10.1074/jbc.M109.098301
- ↑ Nanga RP, Brender JR, Vivekanandan S, Popovych N, Ramamoorthy A. NMR structure in a membrane environment reveals putative amyloidogenic regions of the SEVI precursor peptide PAP(248-286). J Am Chem Soc. 2009 Dec 16;131(49):17972-9. PMID:19995078 doi:10.1021/ja908170s
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