title: Antimicrobial properties of amyloid peptides.
abstract: More than two dozen clinical syndromes known as amyloid diseases are characterized by the buildup of extended insoluble fibrillar deposits in tissues. These amorphous Congo red staining deposits known as amyloids exhibit a characteristic green birefringence and cross-β structure. Substantial evidence implicates oligomeric intermediates of amyloids as toxic species in the pathogenesis of these chronic disease states. A growing body of data has suggested that these toxic species form ion channels in cellular membranes causing disruption of calcium homeostasis, membrane depolarization, energy drainage, and in some cases apoptosis. Amyloid peptide channels exhibit a number of common biological properties including the universal U-shape β-strand-turn-β-strand structure, irreversible and spontaneous insertion into membranes, production of large heterogeneous single-channel conductances, relatively poor ion selectivity, inhibition by Congo red, and channel blockade by zinc. Recent evidence has suggested that increased amounts of amyloids not only are toxic to its host target cells but also possess antimicrobial activity. Furthermore, at least one human antimicrobial peptide, protegrin-1, which kills microbes by a channel-forming mechanism, has been shown to possess the ability to form extended amyloid fibrils very similar to those of classic disease-forming amyloids. In this paper, we will review the reported antimicrobial properties of amyloids and the implications of these discoveries for our understanding of amyloid structure and function.
authors.affiliation: Department of Psychiatry, David Geffen School of Medicine, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, California 90024, USA. bkagan@mednet.ucla.edu
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Kagan
authors.forename: Hyunbum
authors.initials: H
authors.lastname: Jang
authors.forename: Ricardo
authors.initials: R
authors.lastname: Capone
authors.forename: Fernando
authors.initials: F
authors.lastname: Teran Arce
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Ratnesh
authors.initials: R
authors.lastname: Lal
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D004594:Electrophysiology; D006801:Humans
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D000890:Anti-Infective Agents
references.citation: J Neurochem. 1994 Jan;62(1):372-5
references.pmid: 8263540
references.citation: J Lab Clin Med. 2005 Apr;145(4):187-93
references.pmid: 15962837
references.citation: Biophys J. 2010 Jun 2;98(11):2644-52
references.pmid: 20513409
references.citation: Peptides. 2002 Jul;23(7):1215-28
references.pmid: 12128079
references.citation: Am J Physiol Cell Physiol. 2003 Oct;285(4):C862-72
references.pmid: 12814912
references.citation: Structure. 2002 Oct;10(10):1363-70
references.pmid: 12377122
references.citation: J Membr Biol. 2003 May 1;193(1):35-45
references.pmid: 12879164
references.citation: J Mol Biol. 1995 Nov 24;254(2):113-8
references.pmid: 7490736
references.citation: Cell Mol Neurobiol. 2001 Jun;21(3):255-84
references.pmid: 11569537
references.citation: J Neurosci Res. 2000 Oct 1;62(1):120-33
references.pmid: 11002294
references.citation: Arch Microbiol. 1984 Sep;139(1):72-5
references.pmid: 6385903
references.citation: J Physiol. 1999 Jul 15;518 ( Pt 2):359-69
references.pmid: 10381585
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2391-6
references.pmid: 12591960
references.citation: FASEB J. 2004 Jul;18(10):1099-101
references.pmid: 15155566
references.citation: Lab Invest. 2002 Jun;82(6):757-66
references.pmid: 12065686
references.citation: Neurobiol Dis. 2011 Jan;41(1):62-70
references.pmid: 20816785
references.citation: J Biol Chem. 1997 Jan 3;272(1):44-7
references.pmid: 8995224
references.citation: J Neurosci Res. 2000 Apr 1;60(1):65-72
references.pmid: 10723069
references.citation: Mol Cell Biochem. 1994 Nov 23;140(2):119-25
references.pmid: 7898484
references.citation: Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6538-43
references.pmid: 20308552
references.citation: Nature. 1978 Nov 9;276(5684):159-63
references.pmid: 740032
references.citation: Adv Exp Med Biol. 2010;677:150-67
references.pmid: 20687488
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3348-53
references.pmid: 19204293
references.citation: Biochem Biophys Res Commun. 1994 Jul 29;202(2):1142-8
references.pmid: 7519420
references.citation: Q J Med. 1993 Jun;86(6):365-74
references.pmid: 8171184
references.citation: J Am Chem Soc. 2009 Oct 21;131(41):14938-45
references.pmid: 19824733
references.citation: Biochemistry. 2005 Aug 2;44(30):10259-70
references.pmid: 16042403
references.citation: Thorax. 1999 May;54(5):444-51
references.pmid: 10212113
references.citation: FEBS Lett. 1999 Feb 19;445(1):57-62
references.pmid: 10069374
references.citation: Science. 2009 Jul 17;325(5938):328-32
references.pmid: 19541956
references.citation: J Mol Biol. 2004 Jan 23;335(4):1039-49
references.pmid: 14698298
references.citation: Neurobiol Aging. 2004 May-Jun;25(5):619-27
references.pmid: 15172740
references.citation: Amyloid. 2002 Mar;9(1):13-23
references.pmid: 12000193
references.citation: Cell Biochem Biophys. 2002;36(2-3):191-207
references.pmid: 12139405
references.citation: Biochim Biophys Acta. 2009 Aug;1788(8):1600-9
references.pmid: 19394305
references.citation: Proc Natl Acad Sci U S A. 2011 Jun 14;108(24):9821-6
references.pmid: 21628577
references.citation: Biochemistry. 2007 Dec 18;46(50):14369-79
references.pmid: 18031063
references.citation: Science. 1992 Apr 10;256(5054):184-5
references.pmid: 1566067
references.citation: J Mol Biol. 2010 Dec 17;404(5):917-34
references.pmid: 20970427
references.citation: Biophys J. 2004 Apr;86(4):2231-7
references.pmid: 15041662
references.citation: J Neurosci Res. 2000 May 15;60(4):490-4
references.pmid: 10797551
references.citation: Ann Diagn Pathol. 2008 Aug;12(4):235-8
references.pmid: 18620988
references.citation: Amyloid. 2001 Jun;8(2):94-100
references.pmid: 11409039
references.citation: Nature. 2002 Apr 4;416(6880):535-9
references.pmid: 11932745
references.citation: Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):567-71
references.pmid: 8380642
references.citation: J Membr Biol. 2004 Nov;202(1):1-10
references.pmid: 15702375
references.citation: Biophys J. 1997 Jul;73(1):67-75
references.pmid: 9199772
references.citation: J Struct Biol. 2000 Jun;130(2-3):88-98
references.pmid: 10940217
references.citation: Proc Natl Acad Sci U S A. 1990 Jan;87(1):210-4
references.pmid: 1688654
references.citation: Nature. 2004 Oct 14;431(7010):805-10
references.pmid: 15483602
references.citation: Nature. 1996 Jul 11;382(6587):180-2
references.pmid: 8700211
references.citation: J Mol Biol. 1997 Oct 31;273(3):729-39
references.pmid: 9356260
references.citation: J Neurosci. 1993 Apr;13(4):1676-87
references.pmid: 8463843
references.citation: Biophys J. 2009 Dec 2;97(11):3029-37
references.pmid: 19948133
references.citation: Biophys J. 2007 Sep 15;93(6):1938-49
references.pmid: 17526580
references.citation: Nature. 2006 Mar 16;440(7082):352-7
references.pmid: 16541076
references.citation: FASEB J. 2001 Nov;15(13):2433-44
references.pmid: 11689468
references.citation: Trends Neurosci. 1997 Feb;20(2):67-72
references.pmid: 9023874
references.citation: J Mol Biol. 2007 May 11;368(4):982-97
references.pmid: 17382345
references.citation: J Biol Chem. 2008 Aug 1;283(31):21530-9
references.pmid: 18508760
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3453-7
references.pmid: 20142512
references.citation: Neurotox Res. 2009 Jul;16(1):1-13
references.pmid: 19526294
references.citation: Neuroreport. 1994 Oct 27;5(16):2016-8
references.pmid: 7532452
references.citation: J Neurosci Res. 1999 Aug 15;57(4):458-66
references.pmid: 10440895
references.citation: Biophys J. 2008 Nov 15;95(10):4631-42
references.pmid: 18708452
references.citation: Eur J Biochem. 2002 Nov;269(22):5642-8
references.pmid: 12423364
references.citation: Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):571-6
references.pmid: 10639120
references.citation: Nature. 2002 Apr 4;416(6880):507-11
references.pmid: 11932737
references.citation: Biochem Biophys Res Commun. 2005 May 6;330(2):585-90
references.pmid: 15796923
references.citation: J Mol Biol. 2004 Aug 27;341(5):1175-87
references.pmid: 15321714
references.citation: J Alzheimers Dis. 2010;22(2):443-57
references.pmid: 20847430
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10427-32
references.pmid: 16020533
references.citation: Microbiol Rev. 1991 Dec;55(4):733-51
references.pmid: 1779933
references.citation: Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10573-7
references.pmid: 7504270
references.citation: Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1710-5
references.pmid: 8643694
references.citation: Biochim Biophys Acta. 1999 Aug 20;1420(1-2):23-9
references.pmid: 10446287
references.citation: Biophys J. 2011 Apr 6;100(7):1775-83
references.pmid: 21463591
references.citation: Am J Clin Pathol. 2004 Jun;121(6):787-9
references.pmid: 15198347
references.citation: J Neurosci Res. 2001 Oct 15;66(2):214-20
references.pmid: 11592116
references.citation: Br J Ophthalmol. 2005 Jun;89(6):684-8
references.pmid: 15923502
references.citation: J Biol Chem. 1996 Jan 26;271(4):1988-92
references.pmid: 8567648
references.citation: Brain Res. 1997 Jan 2;744(1):7-14
references.pmid: 9030407
references.citation: Neuroreport. 1999 May 14;10(7):1427-31
references.pmid: 10380958
references.citation: PLoS One. 2010 Mar 03;5(3):e9505
references.pmid: 20209079
references.citation: Nature. 2002 Jul 18;418(6895):291
references.pmid: 12124613
references.citation: Biochemistry. 1998 Oct 13;37(41):14563-74
references.pmid: 9772185
references.citation: Nature. 1983 Apr 21;302(5910):709-11
references.pmid: 6300695
references.citation: J Biol Chem. 2003 Oct 17;278(42):40481-92
references.pmid: 12917432
references.citation: Neurobiol Aging. 2004 May-Jun;25(5):629-37
references.pmid: 15172741