title: Understanding the complex mechanisms of β2-microglobulin amyloid assembly.
abstract: Several protein misfolding diseases are associated with the conversion of native proteins into ordered protein aggregates known as amyloid. Studies of amyloid assemblies have indicated that non-native proteins are responsible for initiating aggregation in vitro and in vivo. Despite the importance of these species for understanding amyloid disease, the structural and dynamic features of amyloidogenic intermediates and the molecular details of how they aggregate remain elusive. This review focuses on recent advances in developing a molecular description of the folding and aggregation mechanisms of the human amyloidogenic protein β(2)-microglobulin under physiologically relevant conditions. In particular, the structural and dynamic properties of the non-native folding intermediate I(T) and its role in the initiation of fibrillation and the development of dialysis-related amyloidosis are discussed.
authors: Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA. teichner@brandeis.edu
authors: Timo
authors: T
authors: Eichner
authors: Sheena E
authors: SE
authors: Radford
references: J Biol Chem. 2005 Sep 23;280(38):32843-8
references: 16046408
references: Kidney Int Suppl. 2001 Feb;78:S164-71
references: 11169004
references: Protein Sci. 2005 Mar;14(3):696-702
references: 15689502
references: Semin Dial. 2001 Mar-Apr;14(2):117-22
references: 11264779
references: Biochemistry. 2010 Feb 23;49(7):1522-32
references: 20088607
references: Biochemistry. 2006 Feb 21;45(7):2311-21
references: 16475820
references: Nature. 1997 Feb 27;385(6619):787-93
references: 9039909
references: Nat Struct Mol Biol. 2006 Mar;13(3):195-201
references: 16491092
references: Science. 2009 Dec 4;326(5958):1337-9
references: 19965731
references: N Engl J Med. 1990 Oct 11;323(15):1070-1
references: 2215569
references: J Mol Biol. 2004 Jan 23;335(4):1051-64
references: 14698299
references: J Lab Clin Med. 1991 Aug;118(2):153-65
references: 1856578
references: J Mol Biol. 2008 May 9;378(4):887-97
references: 18395224
references: Biophys J. 2007 Mar 1;92(5):1673-81
references: 17158575
references: Biochemistry. 1996 May 21;35(20):6470-82
references: 8639594
references: Curr Opin Microbiol. 2009 Dec;12(6):623-30
references: 19864176
references: Biochemistry. 2005 Dec 13;44(49):16098-107
references: 16331970
references: Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11622-7
references: 15280548
references: J Biochem. 2011 Jul;150(1):39-47
references: 21398368
references: J Biol Chem. 2005 Oct 28;280(43):35815-21
references: 16105836
references: Proc Natl Acad Sci U S A. 1985 Jun;82(12):4225-9
references: 3889925
references: Protein Sci. 2004 Mar;13(3):797-809
references: 14767076
references: J Mol Biol. 2009 Mar 13;386(5):1312-26
references: 19452600
references: Biochem Biophys Res Commun. 1990 May 16;168(3):1223-9
references: 2189404
references: Anal Chem. 2006 Jun 1;78(11):3667-73
references: 16737222
references: Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2353-8
references: 8637877
references: J Mol Biol. 2005 Mar 25;347(2):323-35
references: 15740744
references: Protein Sci. 2001 Sep;10(9):1775-84
references: 11514668
references: J Biol Chem. 2004 Apr 2;279(14):14111-9
references: 14724277
references: J Mol Biol. 2005 Jul 8;350(2):379-92
references: 15925383
references: Biochem Biophys Res Commun. 2008 Dec 5;377(1):146-50
references: 18835253
references: Mol Cell. 2011 Jul 8;43(1):8-18
references: 21726806
references: J Biol Chem. 2008 Feb 22;283(8):4912-20
references: 18056266
references: J Mol Biol. 2003 Jun 27;330(1):159-74
references: 12818210
references: Nephron. 1991;59(4):654-7
references: 1766508
references: J Biol Chem. 2004 Mar 5;279(10):9176-89
references: 14660575
references: Biochim Biophys Acta. 2005 Nov 10;1753(1):76-84
references: 16081329
references: Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1314-9
references: 21220305
references: J Mol Biol. 2006 Oct 13;363(1):279-88
references: 16959264
references: Biophys J. 2006 Jun 1;90(11):3865-79
references: 16513784
references: Protein Sci. 2000 May;9(5):831-45
references: 10850793
references: Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3147-52
references: 16488975
references: Nat Struct Biol. 2002 Apr;9(4):308-15
references: 11887182
references: Nat Struct Mol Biol. 2006 Mar;13(3):202-8
references: 16491088
references: Biochemistry. 2004 Jun 22;43(24):7808-15
references: 15196023
references: Protein Sci. 2010 Jul;19(7):1386-94
references: 20506535
references: Eur Biophys J. 2006 May;35(5):439-45
references: 16520957
references: J Am Chem Soc. 2010 Dec 8;132(48):17077-9
references: 21077676
references: FEBS J. 2006 Jun;273(11):2461-74
references: 16704420
references: J Am Soc Mass Spectrom. 2009 Feb;20(2):278-86
references: 18996721
references: J Biol Chem. 2005 Mar 25;280(12):12012-8
references: 15659393
references: J Biol Chem. 2010 Feb 19;285(8):5827-35
references: 20028983
references: J Mol Biol. 2005 Aug 26;351(4):910-22
references: 16024042
references: Nat Chem Biol. 2009 Jan;5(1):15-22
references: 19088715
references: Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13373-8
references: 18768806
references: Nephron. 1992;60(3):268-73
references: 1565178
references: J Mol Biol. 2007 Sep 28;372(4):981-991
references: 17681531
references: Prion. 2009 Jan-Mar;3(1):1-4
references: 19377278
references: Biochemistry. 2004 Aug 31;43(34):11075-82
references: 15323566
references: Nat Struct Mol Biol. 2011 Jan;18(1):49-55
references: 21131979
references: Biochim Biophys Acta. 2005 Nov 10;1753(1):44-50
references: 16213198
references: J Mol Biol. 1982 Apr 25;156(4):891-910
references: 6811753
references: Biochemistry. 2005 Mar 22;44(11):4397-407
references: 15766269
references: Biochemistry. 2009 Oct 20;48(41):9871-81
references: 19754160
references: J Mol Biol. 2009 May 29;389(1):48-57
references: 19345691
references: Biochemistry. 2009 Jul 21;48(28):6610-7
references: 19518133
references: J Mol Biol. 2004 Nov 12;344(1):107-18
references: 15504405
references: J Mol Biol. 1999 Oct 15;293(1):67-79
references: 10512716
references: Biophys J. 2009 Jan;96(1):169-79
references: 18835891
references: Eur J Med. 1992 Jul-Aug;1(4):196-200
references: 1341444
references: Kidney Int. 1997 Jan;51(1):187-94
references: 8995733
references: Biochem Biophys Res Commun. 2009 Apr 3;381(2):187-91
references: 19232323
references: J Immunol. 2000 Jun 15;164(12):6398-405
references: 10843695
references: J Mol Biol. 2003 Jul 25;330(5):935-41
references: 12860117
references: J Mol Biol. 2005 Nov 25;354(2):473-82
references: 16242719
references: Protein Sci. 2002 Sep;11(9):2218-29
references: 12192077
references: J Biol Chem. 2006 Oct 13;281(41):31061-9
references: 16901902
references: Biochemistry. 1992 Sep 15;31(36):8654-60
references: 1390650
references: Protein Sci. 2007 Feb;16(2):343-9
references: 17242436
references: Nat Struct Biol. 2003 Jun;10(6):461-7
references: 12754496
references: Nephrol Dial Transplant. 2008 Oct;23(10):3247-55
references: 18467373
references: J Mol Biol. 1982 Apr 25;156(4):911-26
references: 6811754
references: J Mol Biol. 2001 Mar 16;307(1):379-91
references: 11243826
references: Protein Sci. 2009 Aug;18(8):1592-601
references: 19606503
references: J Biochem. 1979 Jun;85(6):1427-38
references: 110798
references: J Mol Biol. 2005 Apr 29;348(2):383-97
references: 15811375
references: J Mol Biol. 2001 Jun 1;309(2):339-45
references: 11371157
references: Protein Sci. 2008 Apr;17(4):748-59
references: 18305198
references: Biochemistry. 2009 Jun 23;48(24):5689-99
references: 19432419
references: Nat Struct Biol. 2000 Sep;7(9):754-7
references: 10966644
references: Kidney Int. 1991 May;39(5):1012-9
references: 2067196
references: J Biol Chem. 2002 Mar 29;277(13):11184-9
references: 11801591
references: J Mol Biol. 2007 Mar 16;367(1):1-7
references: 17254602
references: Biochim Biophys Acta. 2005 Nov 10;1753(1):92-9
references: 16226064
references: Nephrol Dial Transplant. 2009 May;24(5):1593-8
references: 19096084
references: J Biol Chem. 2006 Jun 16;281(24):16521-9
references: 16601119
references: Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10218-10223
references: 16798882
references: Biochem Biophys Res Commun. 2009 Mar 13;380(3):543-7
references: 19284997
references: J Mol Biol. 2005 Feb 25;346(3):773-88
references: 15713462
references: J Mol Biol. 2008 Oct 24;382(5):1242-55
references: 18708068
references: Nat Rev Mol Cell Biol. 2010 Apr;11(4):301-7
references: 20308987
references: J Clin Invest. 1994 Feb;93(2):521-8
references: 8113390
references: Kidney Int. 1986 Sep;30(3):385-90
references: 3537446
references: Eur J Biochem. 1998 Nov 15;258(1):61-7
references: 9851692
references: Biophys J. 2003 Apr;84(4):2149-58
references: 12668424
references: J Biol Chem. 2008 Jun 20;283(25):17279-86
references: 18424782
references: Biochem J. 1991 Jul 1;277 ( Pt 1):175-82
references: 1649598
references: Clin Chem. 2005 Jul;51(7):1177-84
references: 15890888
references: J Biol Chem. 2001 Aug 31;276(35):32657-62
references: 11418618
references: Int Immunol. 2001 Aug;13(8):1063-73
references: 11470776
references: Kidney Int. 2007 Jul;72(2):174-81
references: 17495865
references: Nephrol Dial Transplant. 1995;10(9):1672-8
references: 8559488
references: Annu Rev Biochem. 2006;75:333-66
references: 16756495
references: J Mol Biol. 2003 Jul 25;330(5):943-54
references: 12860118
references: J Am Soc Nephrol. 2004 Jan;15(1):126-33
references: 14694164
references: Curr Opin Struct Biol. 1998 Feb;8(1):101-6
references: 9519302
references: Biochim Biophys Acta. 2005 Nov 10;1753(1):23-33
references: 16154394
references: Biochemistry. 2008 Feb 26;47(8):2650-60
references: 18211100
references: Annu Rev Med. 2006;57:223-41
references: 16409147
references: Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9771-6
references: 12119416
references: Mol Immunol. 2010 Sep;47(15):2519-24
references: 20619457
references: Biochemistry. 2002 Aug 27;41(34):10646-56
references: 12186550
references: J Am Chem Soc. 2010 Aug 4;132(30):10414-23
references: 20662519
references: Mol Cell. 2009 Jun 12;34(5):569-79
references: 19524537
references: Nature. 1990 Apr 19;344(6268):742-6
references: 2139497
references: Nat Struct Mol Biol. 2008 Sep;15(9):965-71
references: 19172750
references: J Mol Biol. 2010 Aug 13;401(2):286-97
references: 20558175
references: Biochim Biophys Acta. 2005 Nov 10;1753(1):34-43
references: 16084781
references: J Biochem. 2007 Sep;142(3):413-9
references: 17646174
references: Nephrol Dial Transplant. 1995;10 Suppl 10:48-51
references: 8825433
references: J Biol Chem. 2010 May 28;285(22):17137-47
references: 20335170
references: J Biol Chem. 2001 Dec 14;276(50):46714-21
references: 11590172
references: Mol Cell. 2011 Jan 21;41(2):161-72
references: 21255727
references: Proteins. 2011 Mar;79(3):986-1001
references: 21287627
references: Protein Sci. 2002 Mar;11(3):487-99
references: 11847272
references: Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1896-901
references: 9050876
references: Biochem J. 2008 Dec 1;416(2):307-15
references: 18637792
references: Semin Dial. 2001 Mar-Apr;14(2):123-6
references: 11264780