The amyloidogenic SEVI precursor, PAP248-286, is highly unfolded in solution despite an underlying helical tendency.
Amyloid fibers in human semen known as SEVI (semen-derived enhancer of viral infection) dramatically increase the infectivity of HIV and other enveloped viruses, which appears to be linked to the promotion of bridging interactions and the neutralization of electrostatic repulsion between the host and the viral cell membranes. The SEVI precursor PAP(248-286) is mostly disordered when bound to detergent micelles, in contrast to the highly α-helical structures found for most amyloid proteins. To determine the origin of this difference, the structures of PAP(248-286) were solved in aqueous solution and with 30% and 50% trifluoroethanol. In solution, pulsed field gradient (PFG)-NMR and (1)H-(1)H NOESY experiments indicate that PAP(248-286) is unfolded to an unusual degree for an amyloidogenic peptide but adopts significantly helical structures in TFE solutions. The clear differences between the structures of PAP(248-286) in TFE and SDS indicate electrostatic interactions play a large role in the folding of the peptide, consistent with the slight degree of penetration of PAP(248-286) into the hydrophobic core of the micelle. This is another noticeable difference between PAP(248-286) and other amyloid peptides, which generally show penetration into at least the headgroup region of the bilayer, and may explain some of the unusual properties of SEVI.
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA.
Jeffrey R
JR
Brender
Ravi Prakash Reddy
RP
Nanga
Nataliya
N
Popovych
Ronald
R
Soong
Peter M
PM
Macdonald
Ayyalusamy
A
Ramamoorthy
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry*; D058767:Protein Unfolding; D012967:Sodium Dodecyl Sulfate / Q000031:analogs & derivatives / Q000737:chemistry; D012996:Solutions; D055672:Static Electricity; D014270:Trifluoroethanol; D014867:Water / Q000737:chemistry
D000682:Amyloid; D008823:Micelles; D010446:Peptide Fragments; D012996:Solutions; D014867:Water; C017948:dodecyltriethoxy sulfate; D012967:Sodium Dodecyl Sulfate; D014270:Trifluoroethanol; C526435:prostatic acid phosphatase (248-286), human; D017027:Protein Tyrosine Phosphatases
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