6UCK

proIAPP in DPC Micelles - Two-Conformer Ensemble Refinement, Bent Conformer

6UCK の概要

• エントリーDOI: 10.2210/pdb6uck/pdb
• 関連するPDBエントリー: 6UA0 6UCJ
• NMR情報: BMRB: 50007
• 分子名称: Islet amyloid polypeptide (1 entity in total)
• 機能のキーワード: membrane-binding, idp, amyloid, hormone
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 8045.18

構造登録者

DeLisle, C.F.,Malooley, A.L.,Banerjee, I.,Lorieau, J.L. (登録日: 2019-09-16, 公開日: 2020-02-26, 最終更新日: 2024-11-20)

主引用文献

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

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: 32077246
DOI: 10.1111/febs.15253

実験手法

SOLUTION NMR