PMID- 29499190
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201123
IS  - 1879-2642 (Electronic)
IS  - 0005-2736 (Linking)
VI  - 1860
IP  - 9
DP  - 2018 Sep
TI  - A single mutation on the human amyloid polypeptide modulates fibril growth and 
      affects the mechanism of amyloid-induced membrane damage.
PG  - 1783-1792
LID - S0005-2736(18)30059-2 [pii]
LID - 10.1016/j.bbamem.2018.02.018 [doi]
AB  - Amyloid fibril formation has been implicated in a wide range of human diseases 
      and the interactions of amyloidogenic proteins with cell membranes are considered 
      to be important in the aetiology of these pathologies. In type 2 diabetes 
      mellitus (T2DM), the human islet amyloid polypeptide (hIAPP) forms amyloid 
      fibrils which impair the functionality and viability of pancreatic beta cells. The 
      mechanisms of hIAPP cytotoxicity are linked to the ability of the peptide to 
      self-aggregate and to interact with membranes. Previous studies have shown that 
      the N-terminal part of hIAPP from residues 1 to 19 is the membrane binding 
      domain. The non-amyloidogenic and nontoxic mouse IAPP differs from hIAPP by six 
      residues out of 37, among which a single one, residue 18, lies in the membrane 
      binding region. To gain more insight into hIAPP-membrane interactions we herein 
      performed comprehensive biophysical studies on four analogues (H18R-IAPP, 
      H18K-IAPP, H18E-IAPP and H18A-IAPP). Our data reveal that all peptides are able 
      to insert efficiently in the membrane, indicating that residue 18 is not 
      essential for hIAPP membrane binding and insertion. However, only wild-type hIAPP 
      and H18K-IAPP are able to form fibrils at the membrane. Importantly, all peptides 
      induce membrane damage; wild-type hIAPP and H18K-IAPP presumably cause membrane 
      disruption mainly by fibril growth at the membrane, while for H18R-IAPP, 
      H18E-IAPP and H18A-IAPP, membrane leakage is most likely due to high molecular 
      weight oligomeric species. These results highlight the importance of the residue 
      at position 18 in IAPP for modulating fibril formation at the membrane and the 
      mechanisms of membrane leakage.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Hoffmann, Anais R F
AU  - Hoffmann ARF
AD  - Sorbonne Universite, Ecole Normale Superieure, PSL University, CNRS, Laboratoire 
      des Biomolecules, 4 place Jussieu, F-75005 Paris, France.
FAU - Saravanan, Manikam Sadasivam
AU  - Saravanan MS
AD  - Department of Chemistry, Faculty of Science, Membrane Biochemistry and 
      Biophysics, Bijvoet Center for Biomolecular Research, Padualaan 8, 3584 Utrecht, 
      The Netherlands.
FAU - Lequin, Olivier
AU  - Lequin O
AD  - Sorbonne Universite, Ecole Normale Superieure, PSL University, CNRS, Laboratoire 
      des Biomolecules, 4 place Jussieu, F-75005 Paris, France.
FAU - Killian, J Antoinette
AU  - Killian JA
AD  - Department of Chemistry, Faculty of Science, Membrane Biochemistry and 
      Biophysics, Bijvoet Center for Biomolecular Research, Padualaan 8, 3584 Utrecht, 
      The Netherlands.
FAU - Khemtemourian, Lucie
AU  - Khemtemourian L
AD  - Sorbonne Universite, Ecole Normale Superieure, PSL University, CNRS, Laboratoire 
      des Biomolecules, 4 place Jussieu, F-75005 Paris, France. Electronic address: 
      lucie.khemtemourian@upmc.fr.
LA  - eng
PT  - Journal Article
DEP - 20180227
PL  - Netherlands
TA  - Biochim Biophys Acta Biomembr
JT  - Biochimica et biophysica acta. Biomembranes
JID - 101731713
SB  - IM
OTO - NOTNLM
OT  - Aggregation kinetics
OT  - Amyloid-membrane interactions
OT  - Islet amyloid polypeptide
OT  - Membrane leakage
OT  - Model membranes (LUV)
OT  - Type 2 diabetes mellitus
EDAT- 2018/03/03 06:00
MHDA- 2018/03/03 06:01
CRDT- 2018/03/03 06:00
PHST- 2017/12/22 00:00 [received]
PHST- 2018/02/19 00:00 [revised]
PHST- 2018/02/20 00:00 [accepted]
PHST- 2018/03/03 06:00 [pubmed]
PHST- 2018/03/03 06:01 [medline]
PHST- 2018/03/03 06:00 [entrez]
AID - S0005-2736(18)30059-2 [pii]
AID - 10.1016/j.bbamem.2018.02.018 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Biomembr. 2018 Sep;1860(9):1783-1792. doi: 
      10.1016/j.bbamem.2018.02.018. Epub 2018 Feb 27.