Abstract
Insights into the three-dimensional structure of hormone fibrils are crucial for a detailed understanding of how an amyloid structure allows the storage of hormones in secretory vesicles prior to hormone secretion into the blood stream. As an example for various hormone amyloids, we have studied the endogenous opioid neuropeptide β-endorphin in one of its fibril forms. We have achieved the sequential assignment of the chemical shifts of the backbone and side-chain heavy atoms of the fibril. The secondary chemical shift analysis revealed that the β-endorphin peptide adopts three β-strands in its fibril state. This finding fosters the amyloid nature of a hormone at the atomic level.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arvan P, Castle D (1998) Sorting and storage during secretory granule biogenesis: looking backward and looking forward. Biochem J 332:593–610
Astbury WT, Dickinson S, Bailey K (1935) The X-ray interpretation of denaturation and the structure of the seed globulins. Biochem J 29(10):2351–2360
Bockmann A et al (2009) Characterization of different water pools in solid-state NMR protein samples. J Biomol NMR 45(3):319–327
Castellani F et al (2003) Determination of solid-state NMR structures of proteins by means of three-dimensional 15N-13C-13C dipolar correlation spectroscopy and chemical shift analysis. Biochemistry 42(39):11476–11483
Cool DR et al (1995) Identification of the sorting signal motif within proopiomelanocortin for the regulated secretory pathway. J Biol Chem 270(15):8723–8729
Eisenberg D, Jucker M (2012) The amyloid state of proteins in human diseases. Cell 148(6):1188–1203
Fowler DM et al (2007) Functional amyloid–from bacteria to humans. Trends Biochem Sci 32(5):217–224
Gerdes HH et al (1989) The primary structure of human secretogranin-Ii, a widespread tyrosine-sulfated secretory granule protein that exhibits low Ph-induced and calcium-induced aggregation. J Biol Chem 264(20):12009–12015
Glombik MM, Gerdes HH (2000) Signal-mediated sorting of neuropeptides and prohormones: secretory granule biogenesis revisited. Biochimie 82(4):315–326
Glombik MM et al (1999) The disulfide-bonded loop of chromogranin B mediates membrane binding and directs sorting from the trans-Golgi network to secretory granules. EMBO J 18(4):1059–1070
Guillemin R et al (1977) beta-Endorphin and adrenocorticotropin are selected concomitantly by the pituitary gland. Science 197(4311):1367–1369
Igumenova TI et al (2004) Assignments of carbon NMR resonances for microcrystalline ubiquitin. J Am Chem Soc 126(21):6720–6727
Luginbuhl P, Szyperski T, Wuthrich K (1995) Statistical basis for the use of C-13-alpha chemical-shifts in protein-structure determination. J Magn Reson Ser B 109(2):229–233
Maji SK et al (2009) Functional amyloids as natural storage of peptide hormones in pituitary secretory granules. Science 325(5938):328–332
Miller F, de Harven E, Palade GE (1966) The structure of eosinophil leukocyte granules in rodents and in man. J Cell Biol 31(2):349–362
Orci L et al (1986) Conversion of proinsulin to insulin occurs coordinately with acidification of maturing secretory vesicles. J Cell Biol 103(6):2273–2281
Schuetz A et al (2010) Protocols for the sequential solid-state NMR spectroscopic assignment of a uniformly labeled 25 kDa protein: HET-s(1–227). ChemBioChem 11(11):1543–1551
Siemer AB et al (2005) High-resolution solid-state NMR spectroscopy of the prion protein HET-s in its amyloid conformation. Angew Chem Int Ed Engl 44(16):2441–2444
Stoller TJ, Shields D (1989) The propeptide of preprosomatostatin mediates intracellular transport and secretion of alpha-globin from mammalian cells. J Cell Biol 108(5):1647–1655
Van Melckebeke H et al (2010) Atomic-resolution three-dimensional structure of HET-s(218-289) amyloid fibrils by solid-state NMR spectroscopy. J Am Chem Soc 132(39):13765–13775
Vranken WF et al (2005) The CCPN data model for NMR spectroscopy: development of a software pipeline. Proteins 59(4):687–696
Wasmer C et al (2008) Amyloid fibrils of the HET-s(218-289) prion form a beta solenoid with a triangular hydrophobic core. Science 319(5869):1523–1526
Wishart DS, Sykes BD (1994) The C-13 chemical-shift index: a simple method for the identification of protein secondary structure using C-13 chemical-shift data. J Biomol NMR 4(2):171–180
Acknowledgments
This work was supported by the Swiss National Foundation and an ETH-internal grant. We would like to thank Diego Sanchez for preparing TEV protease, the MS-Service by Louis Bertschi for MALDI-TOF measurements and Nadezhda Nespovitaya for helping in setting up β-endorphin fibrils.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Seuring, C., Gath, J., Verasdonck, J. et al. Solid-state NMR sequential assignment of the β-endorphin peptide in its amyloid form. Biomol NMR Assign 10, 259–268 (2016). https://doi.org/10.1007/s12104-016-9681-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12104-016-9681-z