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- W3008403521 abstract "Pro‐islet amyloid polypeptide (proIAPP) is the prohormone precursor molecule to IAPP, also known as amylin. IAPP is a calcitonin family peptide hormone that is cosecreted with insulin, and largely responsible for hunger satiation and metabolic homeostasis. Amyloid plaques containing mixtures of mature IAPP and misprocessed proIAPP deposit on, and destroy pancreatic β‐cell membranes, and they are recognized as a clinical hallmark of type 2 diabetes mellitus. In order to better understand the interaction with cellular membranes, we solved the solution NMR structure of proIAPP bound to dodecylphosphocholine micelles at pH 4.5. We show that proIAPP is a dynamic molecule with four α‐helices. The first two helices are contained within the mature IAPP sequence, while the second two helices are part of the C‐terminal prohormone segment (Cpro). We mapped the membrane topology of the amphipathic helices by paramagnetic relaxation enhancement, and we used CD and diffusion‐ordered spectroscopy to identify environmental factors that impact proIAPP membrane affinity. We discuss how our structural results relate to prohormone processing based on the varied pH environments and lipid compositions of organelle membranes within the regulated secretory pathway, and the likelihood of Cpro survival for cosecretion with IAPP. Database The assigned resonances have been deposited in the Biological Magnetic Resonance Bank (BMRB) with accession numbers 50007 and 50019 for proIAPP and Cpro, respectively. The lowest energy structures have been deposited in the Protein Data Bank (PDB) with access codes 6UCJ and 6UCK ." @default.
- W3008403521 created "2020-03-06" @default.
- W3008403521 creator A5018859062 @default.
- W3008403521 creator A5040133983 @default.
- W3008403521 creator A5085806115 @default.
- W3008403521 creator A5090735569 @default.
- W3008403521 date "2020-03-05" @default.
- W3008403521 modified "2023-10-06" @default.
- W3008403521 title "Pro‐islet amyloid polypeptide in micelles contains a helical prohormone segment" @default.
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- W3008403521 doi "https://doi.org/10.1111/febs.15253" @default.
- W3008403521 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32077246" @default.
- W3008403521 hasPublicationYear "2020" @default.
- W3008403521 type Work @default.