Structure and aggregation mechanism of beta(2)-microglobulin (83-99) peptides studied by molecular dynamics simulations.
Many human neurodegenerative diseases are associated with amyloid fibril formation. The human 99-residue beta(2)-microglobulin (beta2m) is one of the most intensively studied amyloid-forming proteins. Recent studies show that the C-terminal fragments 72-99, 83-89, and 91-96 form by themselves amyloid fibrils in vitro and play a significant role in fibrillization of the full-length beta2m protein under acidic pH conditions. In this work, we have studied the equilibrium structures of the 17-residue fragment 83-99 in solution, and investigated its dimerization process by multiple molecular dynamics simulations. We find that an intertwined dimer, with the positions of the beta-strands consistent with the results for the monomer, is a possible structure for two beta2m(83-89) peptides. Based on our molecular-dynamics-generated dimeric structure, a protofibril model is proposed for the full-length beta2m protein.
Liang
Chungwen
C
National Key Surface Physics Laboratory and Department of Physics, Fudan University, Shanghai, China.
Derreumaux
Philippe
P
Wei
Guanghong
G
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry; D001703:Biophysics / Q000379:methods*; D003198:Computer Simulation; D019281:Dimerization; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D001613:beta 2-Microglobulin / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D010455:Peptides; D001613:beta 2-Microglobulin
Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4079-82
16537488
J Mol Biol. 2006 Mar 3;356(4):1049-63
16403526
Rapid Commun Mass Spectrom. 2006;20(11):1628-36
16636995
Annu Rev Biochem. 2006;75:333-66
16756495
Biophys J. 2006 Sep 1;91(5):1638-47
16766615
J Mol Biol. 2006 Sep 15;362(2):355-64
16919295
J Mol Biol. 2006 Sep 22;362(3):567-79
16930617
Curr Opin Chem Biol. 2006 Oct;10(5):445-52
16935548
J Mol Biol. 2007 Feb 9;366(1):275-85
17166516
J Chem Phys. 2007 Feb 14;126(6):065101
17313247
Prion. 2007 Jan-Mar;1(1):3-8
19164927
J Chem Phys. 2007 Jan 14;126(2):025101
17228975
J Mol Biol. 1999 Oct 29;293(3):449-55
10543942
Biochemistry. 2000 Aug 1;39(30):8735-46
10913285
Nat Struct Biol. 2001 Apr;8(4):316-20
11276250
Protein Sci. 2001 Sep;10(9):1775-84
11514668
J Mol Biol. 2001 Oct 26;313(3):559-71
11676539
J Biol Chem. 2002 Jan 11;277(2):1310-5
11687582
Nat Struct Biol. 2002 May;9(5):326-31
11967566
Protein Sci. 2002 Oct;11(10):2362-9
12237458
J Biol Chem. 2002 Nov 8;277(45):43243-6
12215440
J Mol Biol. 2003 Jan 10;325(2):249-57
12488093
J Mol Biol. 2003 Jun 27;330(1):159-74
12818210
Nature. 2003 Aug 14;424(6950):805-8
12917692
Biochemistry. 2003 Nov 25;42(46):13536-40
14622000
Nature. 2003 Dec 18;426(6968):884-90
14685248
Nature. 2003 Dec 18;426(6968):905-9
14685252
J Mol Biol. 2004 Apr 30;338(3):559-71
15081813
Biochemistry. 2004 Jun 22;43(24):7808-15
15196023
Structure. 2004 Jul;12(7):1245-55
15242601
Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10584-9
15249659
J Am Chem Soc. 2004 Sep 22;126(37):11509-16
15366896
Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13786-91
15361578
Biopolymers. 1983 Dec;22(12):2577-637
6667333
N Engl J Med. 1986 Feb 27;314(9):585-6
3080684
Kidney Int. 1992 May;41(5):1416-29
1614057
Nephron. 1996;72(1):9-26
8903856
J Mol Biol. 1997 Oct 31;273(3):729-39
9356260
Eur J Biochem. 1997 Oct 1;249(1):21-6
9363749
J Am Soc Nephrol. 1998 Sep;9(9):1723-35
9727382
Biophys J. 2004 Dec;87(6):3648-56
15377527
J Mol Biol. 2005 Feb 11;346(1):279-94
15663944
Proteins. 2005 Jul 1;60(1):110-7
15849755
Neurochem Int. 2005 Oct;47(5):369-76
16005113
J Am Chem Soc. 2005 Oct 5;127(39):13530-7
16190716
Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14272-7
16176990
FEBS Lett. 2005 Oct 10;579(24):5425-9
16198346
J Mol Biol. 2005 Nov 25;354(2):473-82
16242719
Biochemistry. 2005 Dec 13;44(49):16098-107
16331970
Curr Opin Struct Biol. 2006 Apr;16(2):260-5
16563741