Amyloid Self-Assembly of hIAPP8-20 via the Accumulation of Helical Oligomers, α-Helix to β-Sheet Transition, and Formation of β-Barrel Intermediates.
Algorithms
Amyloid
/ chemistry
Chromatography, High Pressure Liquid
/ methods
Humans
Insulin-Secreting Cells
/ metabolism
Islet Amyloid Polypeptide
/ chemistry
Microscopy, Atomic Force
Microscopy, Electron, Transmission
Molecular Dynamics Simulation
Protein Conformation, beta-Strand
Spectrum Analysis
beta barrels
helical oligomers
helix-to-sheet transitions
human islet amyloid polypeptide
Journal
Small (Weinheim an der Bergstrasse, Germany)
ISSN: 1613-6829
Titre abrégé: Small
Pays: Germany
ID NLM: 101235338
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
05
12
2018
revised:
21
02
2019
pubmed:
26
3
2019
medline:
29
8
2020
entrez:
26
3
2019
Statut:
ppublish
Résumé
The self-assembly of human islet amyloid polypeptide (hIAPP) into β-sheet-rich nanofibrils is associated with the pathogeny of type 2 diabetes. Soluble hIAPP is intrinsically disordered with N-terminal residues 8-17 as α-helices. To understand the contribution of the N-terminal helix to the aggregation of full-length hIAPP, here the oligomerization dynamics of the hIAPP fragment 8-20 (hIAPP8-20) are investigated with combined computational and experimental approaches. hIAPP8-20 forms cross-β nanofibrils in silico from isolated helical monomers via the helical oligomers and α-helices to β-sheets transition, as confirmed by transmission electron microscopy, atomic force microscopy, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, and reversed-phase high performance liquid chromatography. The computational results also suggest that the critical nucleus of aggregation corresponds to hexamers, consistent with a recent mass-spectroscopy study of hIAPP8-20 aggregation. hIAPP8-20 oligomers smaller than hexamers are helical and unstable, while the α-to-β transition starts from the hexamers. Converted β-sheet-rich oligomers first form β-barrel structures as intermediates before aggregating into cross-β nanofibrils. This study uncovers a complete picture of hIAPP8-20 peptide oligomerization, aggregation nucleation via conformational conversion, formation of β-barrel intermediates, and assembly of cross-β protofibrils, thereby shedding light on the aggregation of full-length hIAPP, a hallmark of pancreatic beta-cell degeneration.
Identifiants
pubmed: 30908844
doi: 10.1002/smll.201805166
pmc: PMC6499678
mid: NIHMS1020303
doi:
Substances chimiques
Amyloid
0
Islet Amyloid Polypeptide
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1805166Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM119691
Pays : United States
Informations de copyright
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Références
J Biol Chem. 2000 May 12;275(19):14077-83
pubmed: 10799482
N Engl J Med. 2000 Aug 10;343(6):411-9
pubmed: 10933741
J Mol Biol. 2002 May 3;318(3):863-76
pubmed: 12054829
J Struct Biol. 2003 Mar;141(3):218-27
pubmed: 12648568
J Clin Endocrinol Metab. 2004 Aug;89(8):3629-43
pubmed: 15292279
J Mol Biol. 2004 Aug 27;341(5):1175-87
pubmed: 15321714
Diabetes. 2004 Dec;53 Suppl 3:S233-8
pubmed: 15561917
Biochemistry. 2006 Aug 8;45(31):9496-508
pubmed: 16878984
Methods Enzymol. 2006;412:314-38
pubmed: 17046666
Protein Sci. 2007 Jan;16(1):110-7
pubmed: 17123962
Biophys J. 2007 Jun 1;92(11):4064-77
pubmed: 17307823
Chem Soc Rev. 2007 Aug;36(8):1263-9
pubmed: 17619686
Proteins. 2008 Apr;71(1):207-14
pubmed: 17932914
Biochemistry. 2007 Nov 27;46(47):13505-22
pubmed: 17979302
J Phys Chem B. 2008 Apr 10;112(14):4410-8
pubmed: 18341325
Mol Med. 2008 Jul-Aug;14(7-8):451-64
pubmed: 18368143
RNA. 2008 Jun;14(6):1164-73
pubmed: 18456842
Protein Sci. 2008 Sep;17(9):1467-74
pubmed: 18556473
Bioinformatics. 2008 Sep 1;24(17):1951-2
pubmed: 18579566
Structure. 2008 Jul;16(7):1010-8
pubmed: 18611374
Biochemistry. 2008 Sep 16;47(37):9900-10
pubmed: 18710262
J Am Chem Soc. 2008 Nov 12;130(45):14990-5001
pubmed: 18937465
Biochemistry. 2008 Dec 2;47(48):12689-97
pubmed: 18989932
Phys Biol. 2009 Feb 10;6(1):015005
pubmed: 19208933
J Biol Chem. 2009 May 1;284(18):11982-91
pubmed: 19244249
Annu Rev Biophys. 2009;38:125-52
pubmed: 19416063
Protein Sci. 2009 Jul;18(7):1521-30
pubmed: 19475663
J Mol Biol. 2009 Oct 23;393(2):383-96
pubmed: 19647750
J Am Chem Soc. 2009 Dec 30;131(51):18283-92
pubmed: 19950949
Chem Rev. 2010 Aug 11;110(8):4820-38
pubmed: 20402519
J Chem Phys. 2010 Apr 28;132(16):165103
pubmed: 20441311
Chem Soc Rev. 2010 Sep;39(9):3480-98
pubmed: 20498896
Analyst. 2011 Jan 7;136(1):20-8
pubmed: 20820495
J Am Chem Soc. 2010 Oct 6;132(39):13765-75
pubmed: 20828131
J Am Chem Soc. 2010 Dec 29;132(51):18223-32
pubmed: 21138275
Clin Chim Acta. 2011 Apr 11;412(9-10):785-7
pubmed: 21219896
Nat Chem. 2011 Feb;3(2):172-7
pubmed: 21258392
J Am Chem Soc. 2011 May 18;133(19):7240-3
pubmed: 21517093
J Biol Chem. 2011 Jul 8;286(27):23959-66
pubmed: 21566116
Physiol Rev. 2011 Jul;91(3):795-826
pubmed: 21742788
J Mol Biol. 2012 Aug 10;421(2-3):390-416
pubmed: 22326493
Science. 2012 Mar 9;335(6073):1228-31
pubmed: 22403391
ACS Nano. 2012 May 22;6(5):3907-18
pubmed: 22468743
Biochemistry. 2012 May 1;51(17):3694-703
pubmed: 22486153
J Phys Chem B. 2013 Sep 5;117(35):10149-60
pubmed: 23926957
Biomacromolecules. 2014 Jan 13;15(1):122-31
pubmed: 24313776
Biochim Biophys Acta. 2014 Dec;1838(12):3162-70
pubmed: 25218343
J Phys Chem B. 2015 Feb 26;119(8):3366-76
pubmed: 25646717
Sci Rep. 2015 Feb 04;5:8240
pubmed: 25649462
Nat Struct Mol Biol. 2015 Jun;22(6):499-505
pubmed: 25938662
Biomacromolecules. 2015 Sep 14;16(9):2940-9
pubmed: 26301845
Angew Chem Int Ed Engl. 2015 Nov 23;54(48):14383-7
pubmed: 26440575
Curr Opin Struct Biol. 2016 Apr;37:9-13
pubmed: 26638022
J Am Chem Soc. 2016 Jan 20;138(2):549-57
pubmed: 26700445
Sci Rep. 2016 Jan 14;6:19463
pubmed: 26763863
ACS Chem Neurosci. 2016 Mar 16;7(3):286-96
pubmed: 26815332
Nat Struct Mol Biol. 2016 May;23(5):409-15
pubmed: 27018801
Proc Natl Acad Sci U S A. 2016 Sep 27;113(39):10866-71
pubmed: 27621459
J Phys Chem B. 2016 Nov 23;120(46):11905-11911
pubmed: 27785911
Elife. 2017 Jan 03;6:
pubmed: 28045370
J Chem Theory Comput. 2017 Mar 14;13(3):1454-1461
pubmed: 28157327
Sci Rep. 2017 Mar 13;7:44041
pubmed: 28287098
Chem Soc Rev. 2017 Oct 30;46(21):6492-6531
pubmed: 28702523
Phys Chem Chem Phys. 2017 Oct 25;19(41):28414-28423
pubmed: 29038815
Biomacromolecules. 2017 Dec 11;18(12):4316-4322
pubmed: 29095600
Elife. 2017 Nov 17;6:
pubmed: 29148426
Biochim Biophys Acta Biomembr. 2018 Mar 14;1860(9):1687-1697
pubmed: 29550287
Chem Sci. 2017 Nov 3;9(2):463-474
pubmed: 29619202
Sci Rep. 2018 Jul 9;8(1):10353
pubmed: 29985420
J Am Chem Soc. 2019 Feb 6;141(5):1941-1948
pubmed: 30621387
Biopolymers. 1983 Dec;22(12):2577-637
pubmed: 6667333
Fold Des. 1998;3(6):577-87
pubmed: 9889167