Atomic Structure of the Cross-beta Spine of Islet Amyloid Polypeptide (amylin)

Overview

Journal Protein Sci

Specialty Biochemistry

Date 2008 Jun 17

PMID 18556473

Citations 145

Authors

Jed J W Wiltzius

Stuart A Sievers

Michael R Sawaya

Duilio Cascio

Dmitriy Popov

Christian Riekel

David Eisenberg

Affiliations

Soon will be listed here.

Abstract

Human islet amyloid polypeptide (IAPP or amylin) is a 37-residue hormone found as fibrillar deposits in pancreatic extracts of nearly all type II diabetics. Although the cellular toxicity of IAPP has been established, the structure of the fibrillar form found in these deposits is unknown. Here we have crystallized two segments from IAPP, which themselves form amyloid-like fibrils. The atomic structures of these two segments, NNFGAIL and SSTNVG, were determined, and form the basis of a model for the most commonly observed, full-length IAPP polymorph.

Citing Articles

Anti-diabetic drug pioglitazone reduces Islet amyloid aggregation overload in the Drosophila neuronal cells.

Sharma K, Rai P, Maurya S, Tapadia M Naunyn Schmiedebergs Arch Pharmacol. 2024; .

PMID: 39636405 DOI: 10.1007/s00210-024-03632-4.

Structural Insights into Seeding Mechanisms of hIAPP Fibril Formation.

Suladze S, Sustay Martinez C, Rodriguez Camargo D, Engler J, Rodina N, Sarkar R J Am Chem Soc. 2024; 146(20):13783-13796.

PMID: 38723619 PMC: 11117405. DOI: 10.1021/jacs.3c14233.

On the importance of being amidated: Analysis of the role of the conserved C-terminal amide of amylin in amyloid formation and cytotoxicity.

Yang T, Filippov I, Manathunga L, Baghai A, Marechal A, Raleigh D Biophys Chem. 2024; 307:107168.

PMID: 38367541 PMC: 11223093. DOI: 10.1016/j.bpc.2023.107168.

Interaction of Proteins Involved in Neuronal Proteinopathies.

Kulichikhin K, Malikova O, Zobnina A, Zalutskaya N, Rubel A Life (Basel). 2023; 13(10).

PMID: 37895336 PMC: 10608209. DOI: 10.3390/life13101954.

Amyloid Aggregation and Liquid-Liquid Phase Separation from the Perspective of Phase Transitions.

Zhang Z, Huang G, Song Z, Gatch A, Ding F J Phys Chem B. 2023; 127(28):6241-6250.

PMID: 37414583 PMC: 10404378. DOI: 10.1021/acs.jpcb.3c01426.

References

Kajava A, Aebi U, Steven A . The parallel superpleated beta-structure as a model for amyloid fibrils of human amylin. J Mol Biol. 2005; 348(2):247-52. DOI: 10.1016/j.jmb.2005.02.029. View

Tenidis K, Waldner M, Bernhagen J, Fischle W, Bergmann M, Weber M . Identification of a penta- and hexapeptide of islet amyloid polypeptide (IAPP) with amyloidogenic and cytotoxic properties. J Mol Biol. 2000; 295(4):1055-71. DOI: 10.1006/jmbi.1999.3422. View

Goldsbury C, Cooper G, Goldie K, Muller S, Saafi E, Gruijters W . Polymorphic fibrillar assembly of human amylin. J Struct Biol. 1997; 119(1):17-27. DOI: 10.1006/jsbi.1997.3858. View

Brunger A, Adams P, Clore G, DeLano W, Gros P, Grosse-Kunstleve R . Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr D Biol Crystallogr. 1998; 54(Pt 5):905-21. DOI: 10.1107/s0907444998003254. View

Hossain P, Kawar B, El Nahas M . Obesity and diabetes in the developing world--a growing challenge. N Engl J Med. 2007; 356(3):213-5. DOI: 10.1056/NEJMp068177. View

Saltiel A . New perspectives into the molecular pathogenesis and treatment of type 2 diabetes. Cell. 2001; 104(4):517-29. DOI: 10.1016/s0092-8674(01)00239-2. View

Jones T, Zou J, Cowan S, Kjeldgaard M . Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr A. 1991; 47 ( Pt 2):110-9. DOI: 10.1107/s0108767390010224. View

Moriarty D, Raleigh D . Effects of sequential proline substitutions on amyloid formation by human amylin20-29. Biochemistry. 1999; 38(6):1811-8. DOI: 10.1021/bi981658g. View

Emsley P, Cowtan K . Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr. 2004; 60(Pt 12 Pt 1):2126-32. DOI: 10.1107/S0907444904019158. View

10.

Azriel R, Gazit E . Analysis of the minimal amyloid-forming fragment of the islet amyloid polypeptide. An experimental support for the key role of the phenylalanine residue in amyloid formation. J Biol Chem. 2001; 276(36):34156-61. DOI: 10.1074/jbc.M102883200. View

11.

Fox N, Schrementi J, Nishi M, Ohagi S, Chan S, Heisserman J . Human islet amyloid polypeptide transgenic mice as a model of non-insulin-dependent diabetes mellitus (NIDDM). FEBS Lett. 1993; 323(1-2):40-4. DOI: 10.1016/0014-5793(93)81444-5. View

12.

Jayasinghe S, Langen R . Membrane interaction of islet amyloid polypeptide. Biochim Biophys Acta. 2007; 1768(8):2002-9. DOI: 10.1016/j.bbamem.2007.01.022. View

13.

Cooper G, Willis A, Clark A, Turner R, Sim R, Reid K . Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients. Proc Natl Acad Sci U S A. 1987; 84(23):8628-32. PMC: 299599. DOI: 10.1073/pnas.84.23.8628. View

14.

Hoppener J, Ahren B, Lips C . Islet amyloid and type 2 diabetes mellitus. N Engl J Med. 2000; 343(6):411-9. DOI: 10.1056/NEJM200008103430607. View

15.

Ritzel R, Meier J, Lin C, Veldhuis J, Butler P . Human islet amyloid polypeptide oligomers disrupt cell coupling, induce apoptosis, and impair insulin secretion in isolated human islets. Diabetes. 2006; 56(1):65-71. DOI: 10.2337/db06-0734. View

16.

Green J, Goldsbury C, Mini T, Sunderji S, Frey P, Kistler J . Full-length rat amylin forms fibrils following substitution of single residues from human amylin. J Mol Biol. 2003; 326(4):1147-56. DOI: 10.1016/s0022-2836(02)01377-3. View

17.

Schmitz O, Brock B, Rungby J . Amylin agonists: a novel approach in the treatment of diabetes. Diabetes. 2004; 53 Suppl 3:S233-8. DOI: 10.2337/diabetes.53.suppl_3.s233. View

18.

Westermark P, Engstrom U, Johnson K, Westermark G, Betsholtz C . Islet amyloid polypeptide: pinpointing amino acid residues linked to amyloid fibril formation. Proc Natl Acad Sci U S A. 1990; 87(13):5036-40. PMC: 54256. DOI: 10.1073/pnas.87.13.5036. View

19.

Nishi M, Chan S, Nagamatsu S, Bell G, Steiner D . Conservation of the sequence of islet amyloid polypeptide in five mammals is consistent with its putative role as an islet hormone. Proc Natl Acad Sci U S A. 1989; 86(15):5738-42. PMC: 297705. DOI: 10.1073/pnas.86.15.5738. View

20.

de Koning E, Morris E, Hofhuis F, Posthuma G, Hoppener J, Morris J . Intra- and extracellular amyloid fibrils are formed in cultured pancreatic islets of transgenic mice expressing human islet amyloid polypeptide. Proc Natl Acad Sci U S A. 1994; 91(18):8467-71. PMC: 44627. DOI: 10.1073/pnas.91.18.8467. View