Membrane disordering is not sufficient for membrane permeabilization by islet amyloid polypeptide: studies of IAPP(20-29) fragments

被引:57
作者
Brender, Jeffrey R. [1 ,2 ]
Heyl, Deborah L. [3 ]
Samisetti, Shyamprasad [3 ]
Kotler, Samuel A. [1 ,2 ]
Osborne, Joshua M. [3 ]
Pesaru, Ranadheer R. [3 ]
Ramamoorthy, Ayyalusamy [1 ,2 ]
机构
[1] Univ Michigan, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA
[3] Eastern Michigan Univ, Dept Chem, Ypsilanti, MI 48197 USA
关键词
LIPID-BILAYERS; NMR-SPECTROSCOPY; DIABETES-MELLITUS; A-BETA; FIBRIL FORMATION; PORE FORMATION; PEPTIDE; DISRUPTION; MECHANISM; IAPP;
D O I
10.1039/c3cp44696d
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
A key factor in the development of type II diabetes is the loss of insulin-producing beta-cells. Human islet amyloid polypeptide protein (human-IAPP) is believed to play a crucial role in this process by forming small aggregates that exhibit toxicity by disrupting the cell membrane. The actual mechanism of membrane disruption is complex and appears to involve an early component before fiber formation and a later component associated with fiber formation on the membrane. By comparing the peptide-lipid interactions derived from solid-state NMR experiments of two IAPP fragments that cause membrane disordering to IAPP derived peptides known to cause significant early membrane permeabilization, we show here that membrane disordering is not likely to be sufficient by itself to cause the early membrane permeabilization observed by IAPP, and may play a lesser role in IAPP membrane disruption than expected.
引用
收藏
页码:8908 / 8915
页数:8
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