Simulation of two-dimensional ultraviolet spectroscopy of amyloid fibrils.
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.
Jiang
Jun
J
Chemistry Department, University of California Irvine, Irvine, California, USA.
Abramavicius
Darius
D
Falvo
Cyril
C
Bulheller
Benjamin M
BM
Hirst
Jonathan D
JD
Mukamel
Shaul
S
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
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)
Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14197-202
17502604
Chem Rev. 2009 Jun;109(6):2350-408
19432416
Nat Chem Biol. 2008 Mar;4(3):159-60
18277973
J Am Chem Soc. 2008 May 7;130(18):5852-3
18410104
Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14237-42
17551015
Opt Express. 2009 Oct 12;17(21):18788-93
20372612
Biochemistry. 2006 Jan 17;45(2):498-512
16401079
J Biochem. 2003 Jul;134(1):159-64
12944383
J Am Chem Soc. 2008 Jan 9;130(1):309-17
18067295
J Am Chem Soc. 2009 Sep 23;131(37):13305-14
19715308
J Histochem Cytochem. 1968 Nov;16(11):673-7
5723775
J Am Chem Soc. 2010 Jun 9;132(22):7769-75
20481498
Biophys J. 2003 May;84(5):3326-35
12719262
J Mol Biol. 2005 Nov 4;353(4):804-21
16213524
J Am Chem Soc. 2008 May 28;130(21):6698-9
18459774
J Phys Chem B. 2010 Jun 24;114(24):8270-7
20503991
Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14233-6
17675411
Protein Sci. 2004 Feb;13(2):319-24
14718651
IUBMB Life. 2007 Apr-May;59(4-5):332-45
17505973
J Alzheimers Dis. 2006 Mar;9(1):13-33
16627931
J Mol Biol. 2000 Mar 17;297(1):73-87
10704308
Biomacromolecules. 2009 Sep 14;10(9):2468-75
19678699
Chem Rev. 2008 Apr;108(4):1331-418
18363410
Neurology. 2006 Jan 24;66(2 Suppl 1):S74-8
16432151
Nat Chem Biol. 2009 Jan;5(1):15-22
19088715
Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7720-5
18499799
J Phys Chem B. 2008 Feb 14;112(6):1866-74
18198861
Acc Chem Res. 2009 Apr 21;42(4):553-62
19323494
Nat Med. 2008 Aug;14(8):837-42
18568035
J Comput Chem. 2005 Dec;26(16):1781-802
16222654
Annu Rev Neurosci. 2003;26:267-98
12704221
J Phys Chem B. 1998 Apr 30;102(18):3586-616
24889800
Curr Opin Struct Biol. 2004 Feb;14(1):96-103
15102455
Nat Chem Biol. 2008 Mar;4(3):197-9
18223646
J Comput Chem. 2010 Jan 15;31(1):224-47
19499541
J Phys Chem B. 2009 Sep 3;113(35):12037-49
19496555
Q Rev Biophys. 1998 Feb;31(1):1-39
9717197
Annu Rev Biochem. 2006;75:333-66
16756495
J Phys Chem B. 2009 Aug 13;113(32):11260-73
19618902
Acc Chem Res. 2008 Aug;41(8):1037-47
18646868
Acc Chem Res. 2006 Sep;39(9):594-602
16981675