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Title: Crystal Structures of IAPP Amyloidogenic Segments Reveal a Novel Packing Motif of Out-of-Register Beta Sheets

Journal Article · · Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry

Structural studies of amyloidogenic segments by X-ray crystallography have revealed a novel packing motif, consisting of out-of-register β sheets, which may constitute one of the toxic species in aggregation related diseases. Here we sought to determine the presence of such a motif in islet amyloid polypeptide (IAPP), whose amyloidogenic properties are associated with type 2 diabetes. We determined four new crystal structures of segments within IAPP, all forming steric zippers. Most interestingly, one of the segments in the fibril core of IAPP forms an out-of-register steric zipper. Analysis of this structure reveals several commonalities with previously solved out-of-register fibrils. Furthermore, our results provide additional evidence of out-of-register β sheets as a common structural motif in amyloid aggregates.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)
Grant/Contract Number:
AC02-06CH11357; AG 029430
OSTI ID:
1267462
Journal Information:
Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry, Vol. 120, Issue 26; ISSN 1520-6106
Publisher:
American Chemical SocietyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 50 works
Citation information provided by
Web of Science

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The activities of amyloids from a structural perspective journal November 2016
Molecular mechanics and quantum chemical calculations unveil the combating effect of baicalein on human islet amyloid polypeptide aggregates journal August 2019
Crystallographic insights into the self‐assembly of KLVFF amyloid‐beta peptides journal February 2018
A cationic polymethacrylate-copolymer acts as an agonist for β-amyloid and an antagonist for amylin fibrillation journal January 2019
Extreme amyloid polymorphism in Staphylococcus aureus virulent PSMα peptides text January 2018
Atomic-level evidence for packing and positional amyloid polymorphism by segment from TDP-43 RRM2 journal March 2018
Distinct oligomerization and fibrillization dynamics of amyloid core sequences of amyloid-beta and islet amyloid polypeptide journal January 2017
Atomic structures of fibrillar segments of hIAPP suggest tightly mated β-sheets are important for cytotoxicity journal January 2017
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