European Biophysics Journal

, Volume 41, Issue 9, pp 695–704 | Cite as

Inhibition of semen-derived enhancer of virus infection (SEVI) fibrillogenesis by zinc and copper

  • Sarah R. Sheftic
  • Jessica M. Snell
  • Suman Jha
  • Andrei T. Alexandrescu
Original Paper

Abstract

Semen-derived enhancer of virus infection (SEVI), a naturally occurring peptide fragment of prostatic acid phosphatase, enhances HIV infectivity by forming cationic amyloid fibrils that aid the fusion of negatively charged virion and target cell membranes. Cu(II) and Zn(II) inhibit fibrillization of SEVI in a kinetic assay using the fibril-specific dye ThT. TEM suggests that the metals do not affect fibril morphology. NMR shows that the metals bind to histidines 3 and 23 in the SEVI sequence. ITC experiments indicate that SEVI forms oligomeric complexes with the metals. Dissociation constants are micromolar for Cu(II) and millimolar for Zn(II). Because the Cu(II) and Zn(II) concentrations that inhibit fibrillization are comparable with those found in seminal fluid the metals may modulate SEVI fibrillization under physiological conditions.

Keywords

Intrinsically unfolded peptide Fibrillization inhibitor Sexual transmission Human immunodeficiency virus Histidine ionization Amyloidogenic protein 

Abbreviations

DMSO

Dimethyl sulfoxide

EDTA

Ethylenediaminetetraacetic acid

ITC

Isothermal titration calorimetry

HIV

Human immunodeficiency virus

HSQC

Heteronuclear single-quantum coherence

NMR

Nuclear magnetic resonance

NOESY

Nuclear Overhauser enhancement spectroscopy

PBS

Phosphate-buffered saline

TBS

Tris-buffered saline

TEM

Transmission electron microscopy

ThT

Thioflavin T

TOCSY

Total correlation spectroscopy

SEVI

Semen-derived enhancer of virus infection—in this case, specifically the 248–286 fragment of human prostatic acid phosphatase: PAP248–286

Supplementary material

249_2012_846_MOESM1_ESM.docx (2.3 mb)
Supplementary material 1 (DOCX 2405 kb)

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Copyright information

© European Biophysical Societies' Association 2012

Authors and Affiliations

  • Sarah R. Sheftic
    • 1
  • Jessica M. Snell
    • 1
  • Suman Jha
    • 1
  • Andrei T. Alexandrescu
    • 1
  1. 1.Department of Molecular and Cell BiologyUniversity of ConnecticutStorrsUSA

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