6UCK
proIAPP in DPC Micelles - Two-Conformer Ensemble Refinement, Bent Conformer
Summary for 6UCK
| Entry DOI | 10.2210/pdb6uck/pdb |
| Related | 6UA0 6UCJ |
| NMR Information | BMRB: 50007 |
| Descriptor | Islet amyloid polypeptide (1 entity in total) |
| Functional Keywords | membrane-binding, idp, amyloid, hormone |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 8045.18 |
| Authors | DeLisle, C.F.,Malooley, A.L.,Banerjee, I.,Lorieau, J.L. (deposition date: 2019-09-16, release date: 2020-02-26, Last modification date: 2024-11-20) |
| Primary citation | DeLisle, C.F.,Malooley, A.L.,Banerjee, I.,Lorieau, J.L. Pro-islet amyloid polypeptide in micelles contains a helical prohormone segment. Febs J., 287:4440-4457, 2020 Cited by PubMed 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. PubMed: 32077246DOI: 10.1111/febs.15253 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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