A de novo designed 11 kDa polypeptide: Model for amyloidogenic intrinsically disordered proteins

Natalya I. Topilina; Vladimir V. Ermolenkov; Vitali Sikirzhytski; Seiichiro Higashiya; Igor K. Lednev; John T. Welch

doi:10.1002/bip.21412

A de novo designed 11 kDa polypeptide: Model for amyloidogenic intrinsically disordered proteins

Natalya I. Topilina
, Vladimir V. Ermolenkov
, Vitali Sikirzhytski
, Seiichiro Higashiya
, Igor K. Lednev
, John T. Welch

Chemistry

University at Albany

SUNY Albany

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

A de novo polypeptide GH₆[(GA)₃GY(GA)₃GE]₈GAH₆ (YE₈) has a significant number of identical weakly interacting β-strands with the turns and termini functionalized by charged amino acids to control polypeptide folding and aggregation. YE8 exists in a soluble, disordered form at neutral pH but is responsive to changes in pH and ionic strength. The evolution of YE8 secondary structure has been successfully quantified during all stages of polypeptide fibrillation by deep UV resonance Raman (DUVRR) spectroscopy combined with other morphological, structural, spectral, and tinctorial characterization. The YE8 folding kinetics at pH 3.5 are strongly dependent on polypeptide concentration with a lag phase that can be eliminated by seeding with a solution of folded fibrillar YE8. The lag phase of polypeptide folding is concentration dependent leading to the conclusion that β-sheet folding of the 11-kDa amyloidogenic polypeptide is completely aggregation driven.

Original language	English
Pages (from-to)	607-618
Number of pages	12
Journal	Biopolymers
Volume	93
Issue number	7
DOIs	https://doi.org/10.1002/bip.21412
State	Published - Jul 2010

Keywords

Amyloid fibril
Intrinsically disordered protein
Model repetitive polypeptide
Protein folding and aggregation
Raman spectroscopy

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10.1002/bip.21412

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title = "A de novo designed 11 kDa polypeptide: Model for amyloidogenic intrinsically disordered proteins",

abstract = "A de novo polypeptide GH6[(GA)3GY(GA)3GE]8GAH 6 (YE8) has a significant number of identical weakly interacting β-strands with the turns and termini functionalized by charged amino acids to control polypeptide folding and aggregation. YE8 exists in a soluble, disordered form at neutral pH but is responsive to changes in pH and ionic strength. The evolution of YE8 secondary structure has been successfully quantified during all stages of polypeptide fibrillation by deep UV resonance Raman (DUVRR) spectroscopy combined with other morphological, structural, spectral, and tinctorial characterization. The YE8 folding kinetics at pH 3.5 are strongly dependent on polypeptide concentration with a lag phase that can be eliminated by seeding with a solution of folded fibrillar YE8. The lag phase of polypeptide folding is concentration dependent leading to the conclusion that β-sheet folding of the 11-kDa amyloidogenic polypeptide is completely aggregation driven.",

keywords = "Amyloid fibril, Intrinsically disordered protein, Model repetitive polypeptide, Protein folding and aggregation, Raman spectroscopy",

author = "Topilina, \{Natalya I.\} and Ermolenkov, \{Vladimir V.\} and Vitali Sikirzhytski and Seiichiro Higashiya and Lednev, \{Igor K.\} and Welch, \{John T.\}",

year = "2010",

month = jul,

doi = "10.1002/bip.21412",

language = "English",

volume = "93",

pages = "607--618",

journal = "Biopolymers",

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publisher = "John Wiley and Sons Inc.",

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TY - JOUR

T1 - A de novo designed 11 kDa polypeptide

T2 - Model for amyloidogenic intrinsically disordered proteins

AU - Topilina, Natalya I.

AU - Ermolenkov, Vladimir V.

AU - Sikirzhytski, Vitali

AU - Higashiya, Seiichiro

AU - Lednev, Igor K.

AU - Welch, John T.

PY - 2010/7

Y1 - 2010/7

N2 - A de novo polypeptide GH6[(GA)3GY(GA)3GE]8GAH 6 (YE8) has a significant number of identical weakly interacting β-strands with the turns and termini functionalized by charged amino acids to control polypeptide folding and aggregation. YE8 exists in a soluble, disordered form at neutral pH but is responsive to changes in pH and ionic strength. The evolution of YE8 secondary structure has been successfully quantified during all stages of polypeptide fibrillation by deep UV resonance Raman (DUVRR) spectroscopy combined with other morphological, structural, spectral, and tinctorial characterization. The YE8 folding kinetics at pH 3.5 are strongly dependent on polypeptide concentration with a lag phase that can be eliminated by seeding with a solution of folded fibrillar YE8. The lag phase of polypeptide folding is concentration dependent leading to the conclusion that β-sheet folding of the 11-kDa amyloidogenic polypeptide is completely aggregation driven.

AB - A de novo polypeptide GH6[(GA)3GY(GA)3GE]8GAH 6 (YE8) has a significant number of identical weakly interacting β-strands with the turns and termini functionalized by charged amino acids to control polypeptide folding and aggregation. YE8 exists in a soluble, disordered form at neutral pH but is responsive to changes in pH and ionic strength. The evolution of YE8 secondary structure has been successfully quantified during all stages of polypeptide fibrillation by deep UV resonance Raman (DUVRR) spectroscopy combined with other morphological, structural, spectral, and tinctorial characterization. The YE8 folding kinetics at pH 3.5 are strongly dependent on polypeptide concentration with a lag phase that can be eliminated by seeding with a solution of folded fibrillar YE8. The lag phase of polypeptide folding is concentration dependent leading to the conclusion that β-sheet folding of the 11-kDa amyloidogenic polypeptide is completely aggregation driven.

KW - Amyloid fibril

KW - Intrinsically disordered protein

KW - Model repetitive polypeptide

KW - Protein folding and aggregation

KW - Raman spectroscopy

UR - https://www.scopus.com/pages/publications/77953979171

U2 - 10.1002/bip.21412

DO - 10.1002/bip.21412

M3 - Article

C2 - 20162724

SN - 0006-3525

VL - 93

SP - 607

EP - 618

JO - Biopolymers

JF - Biopolymers

IS - 7

ER -

A de novo designed 11 kDa polypeptide: Model for amyloidogenic intrinsically disordered proteins

Abstract

Keywords

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