title: Simulation of two-dimensional ultraviolet spectroscopy of amyloid fibrils.
abstract: Revealing the structure and aggregation mechanism of amyloid fibrils is essential for the treatment of over 20 diseases related to protein misfolding. Coherent two-dimensional (2D) infrared spectroscopy is a novel tool that provides a wealth of new insight into the structure and dynamics of biomolecular systems. Recently developed ultrafast laser sources are extending multidimensional spectroscopy into the ultraviolet (UV) region, and this opens up new opportunities for probing fibrils. In a simulation study, we show that 2DUV spectra of the backbone of a 32-residue β-amyloid (Aβ(9-40)) fibril associated with Alzheimer's disease and two intermediate prefibrillar structures carry characteristic signatures of fibril size and geometry that could be used to monitor its formation kinetics. The dependence of these signals on the fibril size and geometry is explored. We demonstrate that the dominant features of the β-amyloid fibril spectra are determined by intramolecular interactions within a single Aβ(9-40), and intermolecular interactions at the "external interface" have clear signatures in the fine details of these signals.
authors.affiliation: Chemistry Department, University of California Irvine, Irvine, California, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.forename: Darius
authors.initials: D
authors.lastname: Abramavicius
authors.forename: Cyril
authors.initials: C
authors.lastname: Falvo
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Bulheller
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Hirst
authors.forename: Shaul
authors.initials: S
authors.lastname: Mukamel
mesh_terms: D000042:Absorption; D020816:Amino Acid Motifs; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D002942:Circular Dichroism; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013056:Spectrophotometry, Ultraviolet
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14197-202
references.pmid: 17502604
references.citation: Chem Rev. 2009 Jun;109(6):2350-408
references.pmid: 19432416
references.citation: Nat Chem Biol. 2008 Mar;4(3):159-60
references.pmid: 18277973
references.citation: J Am Chem Soc. 2008 May 7;130(18):5852-3
references.pmid: 18410104
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14237-42
references.pmid: 17551015
references.citation: Opt Express. 2009 Oct 12;17(21):18788-93
references.pmid: 20372612
references.citation: Biochemistry. 2006 Jan 17;45(2):498-512
references.pmid: 16401079
references.citation: J Biochem. 2003 Jul;134(1):159-64
references.pmid: 12944383
references.citation: J Am Chem Soc. 2008 Jan 9;130(1):309-17
references.pmid: 18067295
references.citation: J Am Chem Soc. 2009 Sep 23;131(37):13305-14
references.pmid: 19715308
references.citation: J Histochem Cytochem. 1968 Nov;16(11):673-7
references.pmid: 5723775
references.citation: J Am Chem Soc. 2010 Jun 9;132(22):7769-75
references.pmid: 20481498
references.citation: Biophys J. 2003 May;84(5):3326-35
references.pmid: 12719262
references.citation: J Mol Biol. 2005 Nov 4;353(4):804-21
references.pmid: 16213524
references.citation: J Am Chem Soc. 2008 May 28;130(21):6698-9
references.pmid: 18459774
references.citation: J Phys Chem B. 2010 Jun 24;114(24):8270-7
references.pmid: 20503991
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14233-6
references.pmid: 17675411
references.citation: Protein Sci. 2004 Feb;13(2):319-24
references.pmid: 14718651
references.citation: IUBMB Life. 2007 Apr-May;59(4-5):332-45
references.pmid: 17505973
references.citation: J Alzheimers Dis. 2006 Mar;9(1):13-33
references.pmid: 16627931
references.citation: J Mol Biol. 2000 Mar 17;297(1):73-87
references.pmid: 10704308
references.citation: Biomacromolecules. 2009 Sep 14;10(9):2468-75
references.pmid: 19678699
references.citation: Chem Rev. 2008 Apr;108(4):1331-418
references.pmid: 18363410
references.citation: Neurology. 2006 Jan 24;66(2 Suppl 1):S74-8
references.pmid: 16432151
references.citation: Nat Chem Biol. 2009 Jan;5(1):15-22
references.pmid: 19088715
references.citation: Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7720-5
references.pmid: 18499799
references.citation: J Phys Chem B. 2008 Feb 14;112(6):1866-74
references.pmid: 18198861
references.citation: Acc Chem Res. 2009 Apr 21;42(4):553-62
references.pmid: 19323494
references.citation: Nat Med. 2008 Aug;14(8):837-42
references.pmid: 18568035
references.citation: J Comput Chem. 2005 Dec;26(16):1781-802
references.pmid: 16222654
references.citation: Annu Rev Neurosci. 2003;26:267-98
references.pmid: 12704221
references.citation: J Phys Chem B. 1998 Apr 30;102(18):3586-616
references.pmid: 24889800
references.citation: Curr Opin Struct Biol. 2004 Feb;14(1):96-103
references.pmid: 15102455
references.citation: Nat Chem Biol. 2008 Mar;4(3):197-9
references.pmid: 18223646
references.citation: J Comput Chem. 2010 Jan 15;31(1):224-47
references.pmid: 19499541
references.citation: J Phys Chem B. 2009 Sep 3;113(35):12037-49
references.pmid: 19496555
references.citation: Q Rev Biophys. 1998 Feb;31(1):1-39
references.pmid: 9717197
references.citation: Annu Rev Biochem. 2006;75:333-66
references.pmid: 16756495
references.citation: J Phys Chem B. 2009 Aug 13;113(32):11260-73
references.pmid: 19618902
references.citation: Acc Chem Res. 2008 Aug;41(8):1037-47
references.pmid: 18646868
references.citation: Acc Chem Res. 2006 Sep;39(9):594-602
references.pmid: 16981675