Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Aug 2:5:85.
doi: 10.3389/fnmol.2012.00085. eCollection 2012.

Pore formation by human stefin B in its native and oligomeric states and the consequent amyloid induced toxicity

Gregor Anderluh  1 , Eva Zerovnik
Affiliations

Pore formation by human stefin B in its native and oligomeric states and the consequent amyloid induced toxicity

Gregor Anderluh et al. Front Mol Neurosci. .

Abstract

It is well documented that amyloid forming peptides and proteins interact with membranes and that this correlates with cytotoxicity. To introduce the theme we give a brief description of some amyloidogenic proteins and note their similarities with pore forming toxins (PFTs) and cell penetrating peptides. Human stefin B, a member of the family of cystatins, is an amyloidogenic protein in vitro. This review describes our studies of the interaction of stefin B oligomers and prefibrillar aggregates with model membranes leading to pore formation. We have studied the interaction between human stefin B and artificial membranes of various compositions. We also have prepared distinct sizes and morphologies of stefin B prefibrillar states and assessed their toxicity. Furthermore, we have measured electrical currents through pores formed by stefin B prefibrillar oligomers in a planar lipid bilayer setup. We finally discuss the possible functional and pathological significance of such pores formed by human stefin B.

Keywords: amyloid pore; amyloid toxicity; cystatin B; lipid membranes; toxic oligomers.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Monomers and separated oligomers of human recombinant stefin B-E31 variant. (A) Elution volumes of a sample composed of monomers, dimers, tetramers, and higher oligomers after application to SEC Superdex 75 column. (B) Only higher oligomers (triangles) were shown to insert into lipid monolayers to some degree. (B) modified from Amyloid, Informa Health Care with permission.
Figure 2
Figure 2
Pore formation in planar lipid bilayers by some of the stefin B variants. Pore formation measured by electrophysiological recordings is shown for native wild-type stefin B (A) stefin B-Y31 variant (B) and membrane destabilization by G4R (C). The break of the membrane is denoted by an arrow. Figure modified from FEBS J., John Wiley and Sons with permission.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Anderluh G., Gutierrez-Aguirre I., Rabzelj S., Ceru S., Kopitar-Jerala N., Macek P., Turk V., Zerovnik E. (2005). Interaction of human stefin B in the prefibrillar oligomeric form with membranes. Correlation with cellular toxicity. FEBS J. 272, 3042–3051 10.1111/j.1742-4658.2005.04717.x - DOI - PubMed
    1. Anderluh G., Lakey J. (2010). Proteins: membrane binding and pore formation. Preface. Adv. Exp. Med. Biol. 677, v–vi - PubMed
    1. Anderluh G., Lakey J. H. (2008). Disparate proteins use similar architectures to damage membranes. Trends Biochem. Sci. 33, 482–490 10.1016/j.tibs.2008.07.004 - DOI - PubMed
    1. Anfinsen C. B. (1973). Principles that govern the folding of protein chains. Science 181, 223–230 10.1126/science.181.4096.223 - DOI - PubMed
    1. Arispe N., Pollard H. B., Rojas E. (1996). Zn2+ interaction with Alzheimer amyloid beta protein calcium channels. Proc. Natl. Acad. Sci. U.S.A. 93, 1710–1715 - PMC - PubMed