       Document 0465
 DOCN  M9490465
 TI    Pepstatin A: polymerization of an oligopeptide.
 DT    9411
 AU    Mothes E; Shoeman RL; Traub P; Max-Planck-Institut fur Zellbiologie,
       Ladenburg, Germany.
 SO    Micron. 1994;25(2):189-217. Unique Identifier : AIDSLINE MED/94332557
 AB    Pepstatin A, a pentapeptide with the molecular weight of 686, is a
       naturally occurring inhibitor of aspartyl proteases secreted by
       Streptomyces species. Above a critical concentration of 0.1 mM at low
       ionic strength and neutral pH, it can polymerize into filaments which
       may extend over several micrometers. After negative staining, these
       filaments show a helical substructure with characteristic diameters
       ranging from 6 to 12 nm. Selected images at higher magnification suggest
       the filaments are composed of two intertwined 6 nm strands. This is in
       agreement with the optical diffraction analysis which additionally
       established a periodic pitch of 25 nm for the helical intertwining.
       Rotary shadowing of the pepstatin A filaments clearly demonstrated the
       right-handedness of the helical twist. In physiological salt solution or
       at higher concentrations of pepstatin A, a variety of higher order
       structures were observed, including ribbons, sheets and cylinders with
       both regular and twisted or irregular geometries. Pepstatin A can
       interact with intermediate filament subunit proteins. These proteins
       possess a long, alpha-helical rod domain that forms coiled-coil dimers,
       which through both hydrophobic and ionic interactions form tetramers
       which, in turn, in the presence of physiological salt concentrations,
       polymerize into the 10 nm intermediate filaments. In the absence of
       salt, pepstatin A and intermediate filament proteins polymerize into
       long filaments with a rough surface and a diameter of 15-17 nm. This
       polymerization appears to be primarily driven by nonionic interactions
       between pepstatin A and polymerization-competent forms of intermediate
       filament proteins, resulting in a composite filament.
       Polymerization-incompetent proteolytic fragments of vimentin, lacking
       portions of the head and/or tail domain, failed to copolymerize with
       pepstatin A into long filaments under these conditions. These peptides,
       as well as bovine serum albumin, were found to stick to the surface of
       pepstatin A filaments, ribbons and sheets. Independent evidence for
       direct association of pepstatin A with intermediate filament subunit
       proteins was provided not only by electron microscopy but also by UV
       difference spectra. Pepstatin A loses its ability to inhibit the
       aspartyl protease of the human immunodeficiency virus type 1 following
       polymerization into the higher order structures described here. The
       amazing fact that pepstatin A can spontaneously self-associate to form
       very large polymers seems to be a more rare event for such small
       peptides. The other examples of synthetic or naturally occurring
       oligopeptides discussed in this review which are able to polymerize into
       higher order structures possess a common property, their hydrophobicity,
       often manifested by clusters of valine or isoleucine residues.(ABSTRACT
       TRUNCATED AT 400 WORDS)
 DE    Comparative Study  Intermediate Filament Proteins/*METABOLISM
       Microscopy, Electron  Pepstatins/CHEMISTRY/*METABOLISM
       Polymers/*METABOLISM  JOURNAL ARTICLE  REVIEW  REVIEW, TUTORIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

