Monday, December 14, 2009

J. Am. Chem. Soc., 2009, 131 (49), pp 17972–17979

NMR Structure in a Membrane Environment Reveals Putative Amyloidogenic Regions of the SEVI Precursor Peptide PAP248−286
Ravi P. R. Nanga†, Jeffrey R. Brender†‡, Subramanian Vivekanandan†‡, Nataliya Popovych†‡ and Ayyalusamy Ramamoorthy*†

Semen is the main vector for HIV transmission worldwide. Recently, a peptide fragment (PAP248−286) has been isolated from seminal fluid that dramatically enhances HIV infectivity by up to 4−5 orders of magnitude. PAP248−286 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 PAP248−286 using NMR spectroscopy in SDS micelles, which serve as a model membrane system. PAP248−286, 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 PAP248−286 is unlike most amyloid peptides in that PAP248−286 is mostly disordered when bound to the surface of the micelle, as opposed to the α-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 α-helix from V262−H270 and a dynamic α/310 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.

1 comment:

melaton said...

We can get viral infection if our immune system is not that strong. Thanks for that information,abstract article tackles deeper about membrane and peptides.