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Journal article
Distinct Modes of Action of IAPP Oligomers on Membranes
Journal of chemical information and modeling, v 61(9), pp 4645-4655
27 Sep 2021
PMID: 34499498
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Islet amyloid polypeptide (IAPP, also known as amylin) is a peptide hormone that is co-secreted with insulin by pancreatic β-cells and forms amyloid aggregates in type II diabetes. Various lines of evidence indicate that oligomers of this peptide may induce toxicity by disrupting or forming pores in cell membranes, but the structure of these pores is unknown. Here, we create models of pores for both helical and β-structured peptides using implicit membrane modeling and test their stability using multimicrosecond all-atom simulations. We find that the helical peptides behave similarly to antimicrobial peptides; they remain stably inserted in a highly tilted or partially unfolded configuration creating a narrow water channel. Parallel helix orientation creates a somewhat larger pore. An octameric β barrel of parallel β-hairpins is highly stable in the membrane, whereas the corresponding barrel made of antiparallel hairpins is not. We propose that certain experiments probe the helical pore state while others probe the β-structured pore state; this provides a possible explanation for lack of correlation that is sometimes observed between in vivo toxicity and in vitro liposome permeabilization experiments.
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Details
- Title
- Distinct Modes of Action of IAPP Oligomers on Membranes
- Creators
- Aliasghar Sepehri - City College of New YorkBinod Nepal - City College of New YorkThemis Lazaridis - City College of New York
- Publication Details
- Journal of chemical information and modeling, v 61(9), pp 4645-4655
- Publisher
- American Chemical Society
- Number of pages
- 11
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000703339100045
- Scopus ID
- 2-s2.0-85115910883
- Other Identifier
- 991021955787204721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Chemistry, Medicinal
- Chemistry, Multidisciplinary
- Computer Science, Information Systems
- Computer Science, Interdisciplinary Applications