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Atomic structures of IAPP (amylin) fusions suggest a mechanism for fibrillation and the role of insulin in the process
Article first published online: 29 APR 2009
DOI: 10.1002/pro.145
Copyright © 2009 The Protein Society
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How to Cite
Wiltzius, J. J. W., Sievers, S. A., Sawaya, M. R. and Eisenberg, D. (2009), Atomic structures of IAPP (amylin) fusions suggest a mechanism for fibrillation and the role of insulin in the process. Protein Science, 18: 1521–1530. doi: 10.1002/pro.145
Publication History
- Issue published online: 23 JUN 2009
- Article first published online: 29 APR 2009
- Accepted manuscript online: 29 APR 2009 12:00AM EST
- Manuscript Accepted: 9 APR 2009
- Manuscript Revised: 7 APR 2009
- Manuscript Received: 13 FEB 2009
Funded by
- NIH
- NSF
- HHMI
References
- 1, , ( 2007) Obesity and diabetes in the developing world—a growing challenge. N Engl J Med 356: 213–215.
- 2( 2001) New perspectives into the molecular pathogenesis and treatment of type 2 diabetes. Cell 104: 517–529.
- 3( 1994) Amylin compared with calcitonin gene-related peptide: structure, biology, and relevance to metabolic disease. Endocr Rev 15: 163–201.
- 4, , , , , ( 1987) Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients. PNAS 84: 8628–8632.
- 5, , , , , ( 1987) Amyloid fibrils in human insulinoma and islets of langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells. PNAS 84: 3881–3885.
- 6, , ( 2004) Amylin agonists: a novel approach in the treatment of diabetes. Diabetes 53: S233–S238.
- 7, , , , ( 2006) Design of a mimic of nonamyloidogenic and bioactive human islet amyloid polypeptide (IAPP) as nanomolar affinity inhibitor of IAPP cytotoxic fibrillogenesis. PNAS 103: 2046–2051.
- 8, , , , ( 2002) Role of islet amyloid in type 2 diabetes mellitus: consequence or cause? Mol Cell Endocrinol 197: 205–212.
- 9, , ( 2000) Islet Amyloid and Type 2 Diabetes Mellitus. N Engl J Med 343: 411–419.
- 10, , , , , , , ( 2005) Islet amyloid polypeptide gene promoter polymorphisms are not associated with Type 2 diabetes or with the severity of islet amyloidosis. Biochim Biophys Acta 1740: 74–78.
- 11, , , , , , , , ( 1994) Intra- and extracellular amyloid fibrils are formed in cultured pancreatic islets of transgenic mice expressing human islet amyloid polypeptide. PNAS 91: 8467–8471.
- 12( 2001) Amyloidogenicity and cytotoxicity of islet amyloid polypeptide. Pept Sci 60: 438–459.
- 13, , , , ( 2006) The aggregation potential of human amylin determines its cytotoxicity towards islet βeta-cells. FEBS J 273: 3614–3624.Direct Link:
- 14, , , , ( 2007) Human islet amyloid polypeptide oligomers disrupt cell coupling, induce apoptosis, and impair insulin secretion in isolated human islets. Diabetes 56: 65–71.
- 15, , , , ( 1989) Conservation of the sequence of islet amyloid polypeptide in five mammals is consistent with its putative role as an islet hormone. PNAS 86: 5738–5742.
- 16, , , , , , , , , ( 1993) Human islet amyloid polypeptide transgenic mice as a model of non-insulin-dependent diabetes mellitus (NIDDM). FEBS Lett 323: 40–44.
- 17( 1989) The insulin secretory granule. Diabetologia 32: 271–289.
- 18, , , , ( 1990) Islet amyloid polypeptide. A new beta cell secretory product related to islet amyloid deposits. J Biol Chem 265: 4173–4176.
- 19, , , , ( 1996) Effects of beta cell granule components on human islet amyloid polypeptide fibril formation. FEBS Lett 379: 203–206.
- 20, ( 2004) The mechanism of insulin action on islet amyloid polypeptide fiber formation. J Mol Biol 335: 221–231.
- 21, , ( 2004a) Pancreatic beta-cell granule peptides form heteromolecular complexes which inhibit islet amyloid polypeptide fibril formation. Biochem J 377: 709–716.
- 22, , ( 2006) Molecular mapping of the recognition interface between the islet amyloid polypeptide and insulin. Angew Chem Int Ed 45: 6476–6480.Direct Link:
- 23, ( 2005) Contribution of the intrinsic disulfide to the assembly mechanism of islet amyloid. Protein Sci 14: 231–239.Direct Link:
- 24, , , , , , ( 1999) Conformational transitions of islet amyloid polypeptide (IAPP) in amyloid formation in Vitro. J Mol Biol 287: 781–796.
- 25, ( 2001) Islet amyloid and type 2 diabetes: from molecular misfolding to islet pathophysiology. Biochim Biophys Acta 1537: 179–203.
- 26, ( 2007) Direct detection of transient α-helical states in islet amyloid polypeptide. Protein Sci 16: 110–117.Direct Link:
- 27, , , , , , , , ( 2000) Amyloid fibril formation from full-length and fragments of amylin. J Struct Biol 130: 352–362.
- 28, , , , , ( 2007) Mechanism of islet amyloid polypeptide fibrillation at lipid interfaces studied by infrared reflection absorption spectroscopy. Biophys J 93: 3132–3141.
- 29, , , , ( 2008) Amylin proprotein processing generates progressively more amyloidogenic peptides that initially sample the helical state. Biochemistry 47: 9900–9910.
- 30, , , , ( 2009) Two-dimensional infrared spectroscopy provides evidence of an intermediate in the membrane-catalyzed assembly of diabetic amyloid. J Phys Chem B 113: 2498–2505.
- 31, , , , , , ( 1994) β-structure in human amylin and 2 designer β-peptides: CD and NMR spectroscopic comparisons suggest soluble β-oligomers and the absence of significant populations of β-strand dimers. Biochem Biophys Res Commun 204: 1088–1095.
- 32, ( 2002) Islet amyloid: phase partitioning and secondary nucleation are central to the mechanism of fibrillogenesis. Biochemistry 41: 4694–4703.
- 33, ( 2004) Phospholipid catalysis of diabetic amyloid assembly. J Mol Biol 341: 1175–1187.
- 34, ( 2005) Lipid membranes modulate the structure of islet amyloid polypeptide. Biochemistry 44: 12113–12119.
- 35, , ( 2008) Structure of α-helical membrane-bound human islet amyloid polypeptide and its implications for membrane-mediated misfolding. J Biol Chem 283: 17205–17210.
- 36, , , , ( 2008) Structures of rat and human islet amyloid polypeptide IAPP1-19 in micelles by NMR spectroscopy. Biochemistry 47: 12689–12697.
- 37, ( 2003) Insights into binding cooperativity of MATa1/MATα2 from the crystal structure of a MATa1 homeodomain-maltose binding protein chimera. Protein Sci 12: 306–312.Direct Link:
- 38, , , , , , ( 2003) Protein-protein docking with simultaneous optimization of rigid-body displacement and side-chain conformations. J Mol Biol 331: 281–299.
- 39, , , ( 1993) Evaluation of secondary structure of proteins from UV circular dichroism spectra using an unsupervised learning neural network. Protein Eng 6: 383–390.
- 40, , , ( 2002) Identification and characterization of a novel molecular-recognition and self-assembly domain within the islet amyloid polypeptide. J Mol Biol 322: 1013–1024.
- 41, , , , ( 1996) Circular dichroism spectrum of a peptide 310-Helix. J Am Chem Soc 118: 2744–2745.
- 42, , , ( 2009) The dynamic α-helix structure of micelle-bound human amylin. J Biol Chem. 284: 11982–11991.
- 43, , , , , , ( 2001) Identification of a novel human islet amyloid polypeptide β-sheet domain and factors influencing fibrillogenesis. J Mol Biol 308: 515–525.
- 44, , , ( 1991) Solution structure of human calcitonin gene-related peptide by proton NMR and distance geometry with restrained molecular dynamics. Biochemistry 30: 575–582.
- 45, ( 1994) Modelling the structure of the calcitonin gene-related peptide. Protein Eng 7: 1069–1075.
- 46, , ( 2009) Residual structure in islet amyloid polypeptide mediates its interactions with soluble insulin. Biochemistry 48: 2368–2376.
- 47, , , , , , ( 2008) Atomic structure of the cross-β spine of islet amyloid polypeptide (amylin). Protein Sci 17: 1467–1474.Direct Link:
- 48, , ( 2006) Conserved and cooperative assembly of membrane-bound α-helical states of islet amyloid polypeptide. Biochemistry 45: 9496–9508.
- 49, , , , , , ( 2000) S20G Mutant amylin exhibits increased in vitro amyloidogenicity and increased intracellular cytotoxicity compared to wild-type amylin. Am J Pathol 157: 2101–2109.
- 50, , ( 1997) Processing of X-ray diffraction data collected in oscillation mode. In CarterJW, SweetRM (eds). Methods in Enzymology: Macromolecular Crystallography, Part A. Academic Press, 276, 307–326.
- 51, , ( 2004) Likelihood-enhanced fast rotation functions. Acta Crystallogr D Biol Crystallogr 60: 432–438.Direct Link:
- 52Collaborative Computational Project ( 1994) The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr 50: 760–763.Direct Link:
- 53, ( 2004) Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60: 2126–2132.Direct Link:

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