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An Unstructured Region is Required by GAV Homologue for the Fibrillization of Host Proteins

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Abstract

Accumulating evidence shows that some amyloidogenic proteins contain core sequences, which are critical for their fibrillization. Core sequences of α-synuclein, β-amyloid peptide and prion protein usually reside in their unfolded regions and share a conserved consensus (VGGAVVAGV) designated as GAV homologue. Here we investigate the role of unfolded regions in fibrillization after GAV homologue is attached to the C-terminus or inserted into the loop regions of different host proteins, namely α -Syn1-65, γ-synuclein, E. coli thioredoxin and immunoglobulin G binding B1 domain of streptococcal protein G. The results imply that an unstructured region is required by GAV homologue for the fibrillization of host proteins. A number of amyloidogenic proteins with core sequences located in unstructured regions are summarized and discussed in details. The finding may provide further insight into the elucidating of the molecular mechanism underlying the fibrillization of α-Syn, Aβ and PrP as well as other amyloidogenic proteins.

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Abbreviations

Aβ:

β-amyloid peptide

AD:

Alzheimer’s disease

AFM:

atomic force microscopy

Ala:

alanine

CD:

circular dichroism

FPLC:

fast protein liquid chromatography

GdmCl:

guanidium chloride

Gly:

glycine

HD:

Huntington’s disease

IAPP:

islet amyloid polypeptide

NAC:

non-Aβ component

OPMD:

oculopharyngeal muscular dystrophy

PABP2:

poly(A) binding protein 2

PBS:

phosphate-buffered saline

PD:

Parkinson’s disease

PGBD:

immunoglobulin G binding B1 protein of streptococcal protein G

PrD:

prion diseases

PrP:

prion protein

SBMA:

spinal and bulbar muscular atrophy

SCA3/MJD:

spino-cerebellar ataxia/Machado-Joseph disease

SDS-PAGE:

sodium dodecyl sulfate polyacrylamide gel electrophoresis

α-Syn:

human α-synuclein

γ-Syn:

human γ-synuclein

ThT:

thioflavin T

TRX:

thioredoxin

UV:

ultra-violet

Val:

Valine

WT:

wild type

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Authors and Affiliations

  1. Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, P.R. China

    Li-Na Ji, Hai-Ning Du, Hong-Tao Li, Xiao-Ying Luo & Hong-Yu Hu

  2. Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, P.R. China

    Li-Na Ji, Feng Zhang & Jun Hu

  3. Bio-X Research Center, Shanghai Jiaotong University, Shanghai, 200030, P.R. China

    Jun Hu

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  1. Li-Na Ji
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  2. Hai-Ning Du
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  3. Feng Zhang
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  4. Hong-Tao Li
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  6. Jun Hu
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Correspondence to Hong-Yu Hu.

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Ji, LN., Du, HN., Zhang, F. et al. An Unstructured Region is Required by GAV Homologue for the Fibrillization of Host Proteins. Protein J 24, 209–218 (2005). https://doi.org/10.1007/s10930-005-6713-4

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