Enhanced<i>in vitro</i>production of amyloid-like fibrils from mutant (S20G) islet amyloid polypeptide

Mao, Zhi; Westermark, Gunilla T.; Sakagashira, Setsuya; Sanke, Tokio; Gustavsson, Åsa; Sakamoto, Haruhiko; Engström, Ulla; Nanjo, Kishio; Westermark, Per

doi:10.3109/13506120108993820

Cited by 58 publications

(81 citation statements)

References 30 publications

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“…S3 and Table S1), which agreed with the previous reports [16,17]. It is of interest to note that spectra showed modest differences in the region of 210-230 nm between the hIAPP and pIAPP fragments, where spectra of hIAPP (20)(21)(22)(23)(24)(25)(26)(27)(28)(29) and hIAPP (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) showed more positive CD signals than those of pIAPP (20)(21)(22)(23)(24)(25)(26)(27)(28)(29) and pIAPP (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) (Fig. 2A...…”

Section: Secondary Structures Determination By Far-uv CD and Spectra supporting

confidence: 89%

“…Our results suggested that both 17D and 18R substitutions show minor impacts on the fibrillation of hIAPP (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). For hIAPP (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) carrying single 17D mutation or 17D18R double mutations, slightly lengthened lag times of 66.9 ± 12.9 min and 64.7 ± 17.5 min were observed as compared with the control hIAPP(17-29) (39.1 ± 10.0 min) ( Table 1). In contrast, 20R-hIA-PP(17-29) showed a dramatically prolonged lag time compared with hIAPP(17-29) (241.5 ± 114.0 min vs. 39.1 ± 10.0 min).…”

Section: Amyloid Formationmentioning

confidence: 58%

“…All decapeptides (IAPP (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)) and tridecapeptides (IAPP (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)) were manually synthesized using standard 9-fluorenylmethyl chloroformate-based solid-phase peptide synthesis (SPPS) methodology as we previously described [8]. Crude peptides were purified by reverse phase high performance liquid chromatography using C4 semi-preparative or analytical column (Kromasil, AkzoNobel, Netherlands), and their identities were confirmed by ESI-MS.…”

Section: Peptide Synthesis and Purificationmentioning

confidence: 99%

“…Among these sites, 17D and 20R exist only in porcine, whereas 18R is also present in species like rodent, chicken and feline. To test their impacts on the amyloidogenicity of IAPP, fourteen analogs were synthesized in IAPP (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) templates (human or porcine, Supplementary Fig. S1).…”

Section: Amyloid Formationmentioning

confidence: 99%

“…1) may affect the amyloidogenicity in the IAPP (20)(21)(22)(23)(24)(25)(26)(27)(28)(29) template. ThT-fluorescence and TEM assays suggested that hIAPP(20-29) readily gave strong ThT fluorescence emission and formed long-linear amyloid fibrils with a short lag time of 39.6 ± 15.7 min (Fig.…”

Section: Amyloid Formationmentioning

confidence: 99%

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Porcine islet amyloid polypeptide fragments are refractory to amyloid formation

et al. 2010

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a b s t r a c tOf 10 variation sites between sequences of amyloid-resistant porcine islet amyloid polypeptide (pIAPP) and amyloid-prone human IAPP (hIAPP), seven locate within residues 17-29, the most amyloidogenic fragment within hIAPP. To investigate how these variations affect amyloidogenicity, 26 IAPP(17-29) or IAPP(20-29) variants were synthesized and their secondary structures, amyloidogenicity, oligomerization and cytotoxicity were studied. Our results indicated that pIAPP fragments are refractory to amyloid formation and significantly less cytotoxic compared with hIAPP fragments. A novel stable dimer was observed in pIAPP(20-29) solution, whereas hIAPP(20-29) exists mostly as monomers and trimers. Among all human to porcine substitutions, S20R caused the most prolonged lag time and significantly attenuated cytotoxicity. The different oligomerization and amyloidogenic properties of hIAPP and pIAPP fragments are discussed.

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Section: Secondary Structures Determination By Far-uv CD and Spectra supporting

confidence: 89%

Section: Amyloid Formationmentioning

confidence: 58%

Section: Peptide Synthesis and Purificationmentioning

confidence: 99%

Section: Amyloid Formationmentioning

confidence: 99%

Section: Amyloid Formationmentioning

confidence: 99%

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Porcine islet amyloid polypeptide fragments are refractory to amyloid formation

et al. 2010

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Amyloidogenicity and cytotoxicity of islet amyloid polypeptide

Kapurniotu

2001

Biopolymers

113

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Insoluble amyloid formation by islet amyloid polypeptide (IAPP) in the islets of Langerhans of the pancreas is a major pathophysiological feature of noninsulin dependent diabetes mellitus (NIDDM) or type II diabetes. Because in vivo formed amyloid colocalizes with areas of cell degeneration and IAPP amyloid aggregates are cytotoxic per se, the process of IAPP amyloid formation has been strongly associated with the progressive pancreatic cell degeneration and thus much of the pathology of type II diabetes. IAPP is a pancreatic polypeptide of 37 residues that, in its soluble form, is believed to play a role as a regulator of glucose homeostasis. The molecular cause and mechanism of the conversion of soluble IAPP into insoluble amyloid aggregates in vivo and its role in disease progress still remain to be clarified. Nevertheless, in the past few years significant progress has been made in understanding the amyloidogenesis pathway of IAPP in vitro and gaining insight into the structural and conformational “requirements” of IAPP amyloidogenesis and related cytotoxic effects. Importantly, several of the studies have revealed significant similarities of the above features of IAPP to other amyloidogenic polypeptides such as the β‐amyloid polypeptide Aβ. This suggests that, at the molecular level, amyloidogenesis, and possibly related cell degeneration and disease pathogenesis by completely different polypeptide sequences, may obey to common structural and conformational “rules” and follow similar molecular pathways. This review describes studies on the structural and conformational features of IAPP amyloid formation and cytotoxicity, and the application of the obtained knowledge for the understanding of the molecular mechanism of the IAPP amyloidogenesis pathway and the related cytotoxicity. © 2002 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 60: 438–459, 2001

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Islet Amyloid Polypeptide

Abedini

Raleigh

2010

Protein Misfolding Diseases

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Enhancedin vitroproduction of amyloid-like fibrils from mutant (S20G) islet amyloid polypeptide

Cited by 58 publications

References 30 publications

Porcine islet amyloid polypeptide fragments are refractory to amyloid formation

Porcine islet amyloid polypeptide fragments are refractory to amyloid formation

Amyloidogenicity and cytotoxicity of islet amyloid polypeptide

Islet Amyloid Polypeptide

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