PMID- 26193839
OWN - NLM
STAT- MEDLINE
DCOM- 20160329
LR  - 20231111
IS  - 1364-5528 (Electronic)
IS  - 0003-2654 (Print)
IS  - 0003-2654 (Linking)
VI  - 140
IP  - 20
DP  - 2015 Oct 21
TI  - Insights into the consequences of co-polymerisation in the early stages of IAPP 
      and Abeta peptide assembly from mass spectrometry.
PG  - 6990-9
LID - 10.1039/c5an00865d [doi]
AB  - The precise molecular mechanisms by which different peptides and proteins 
      assemble into highly ordered amyloid deposits remain elusive. The fibrillation of 
      human amylin (also known as islet amyloid polypeptide, hIAPP) and the 
      amyloid-beta peptide (Abeta-40) are thought to be pathogenic factors in Type 2 
      diabetes mellitus (T2DM) and Alzheimer's disease (AD), respectively. Amyloid 
      diseases may involve co-aggregation of different protein species, in addition to 
      the self-assembly of single precursor sequences. Here we investigate the 
      formation of heterogeneous pre-fibrillar, oligomeric species produced by the 
      co-incubation of hIAPP and Abeta-40 using electrospray ionisation-ion mobility 
      spectrometry-mass spectrometry (ESI-IMS-MS)-based methods. Conformational 
      properties and gas-phase stabilities of amyloid oligomers formed from hIAPP or 
      Abeta40 alone, and from a 1 : 1 mixture of hIAPP and Abeta40 monomers, were determined 
      and compared. We show that co-assembly of the two sequences results in 
      hetero-oligomers with distinct properties and aggregation kinetics properties 
      compared with the homo-oligomers present in solution. The observations may be of 
      key significance to unravelling the mechanisms of amyloid formation in vivo and 
      elucidating how different sequences and/or assembly conditions can result in 
      different fibril structures and/or pathogenic outcomes.
FAU - Young, Lydia M
AU  - Young LM
AD  - Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular 
      Biology, University of Leeds, LS2 9JT, UK. s.e.radford@leeds.ac.uk 
      a.e.ashcroft@leeds.ac.uk.
FAU - Mahood, Rachel A
AU  - Mahood RA
FAU - Saunders, Janet C
AU  - Saunders JC
FAU - Tu, Ling-Hsien
AU  - Tu LH
FAU - Raleigh, Daniel P
AU  - Raleigh DP
FAU - Radford, Sheena E
AU  - Radford SE
FAU - Ashcroft, Alison E
AU  - Ashcroft AE
LA  - eng
GR  - BB/H014713/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - BB/F01614X/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - BB/E012558/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - R01 GM078114/GM/NIGMS NIH HHS/United States
GR  - GM078114/GM/NIGMS NIH HHS/United States
GR  - BB/I015361/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Analyst
JT  - The Analyst
JID - 0372652
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-40))
SB  - IM
MH  - Amino Acid Sequence
MH  - Amyloid beta-Peptides/*chemistry
MH  - Humans
MH  - Islet Amyloid Polypeptide/*chemistry
MH  - Molecular Sequence Data
MH  - Peptide Fragments/*chemistry
MH  - *Protein Multimerization
MH  - Protein Stability
MH  - Protein Structure, Secondary
MH  - *Spectrometry, Mass, Electrospray Ionization
PMC - PMC4626081
MID - NIHMS710267
EDAT- 2015/07/22 06:00
MHDA- 2016/03/30 06:00
PMCR- 2016/10/21
CRDT- 2015/07/22 06:00
PHST- 2015/07/22 06:00 [entrez]
PHST- 2015/07/22 06:00 [pubmed]
PHST- 2016/03/30 06:00 [medline]
PHST- 2016/10/21 00:00 [pmc-release]
AID - 10.1039/c5an00865d [doi]
PST - ppublish
SO  - Analyst. 2015 Oct 21;140(20):6990-9. doi: 10.1039/c5an00865d.