Salient Structural Features of Low Molecular Weight Amyloid Fibril Proteins in Familial Amyloid Polyneuropathy of Japanese Origin

SummaryAs part of a more extensive investigation on structural features of different low-molecular-weight heparins (LMWHs) that can affect their biological activities, Enoxaparin,Tinzaparin and Dalteparin were characterised with regards to the distribution of different chain length oligosaccharides as determined by size-exclusion (SE) chromatography, as well as their structure as defined by 2D-NMR spectra (HSQC). The three LMWHs were also fractionated into high affinity (HA) and no affinity (NA) pools with regards to their ability to bind antithrombin (AT).The HA fractions were further subfractionated and characterised. For the parent LMWHs and selected fractions,molecular weight parameters were measured using a SE chromatographic system with a triple detector (TDA) to obtain absolute molecular weights. The SE chromatograms clearly indicate that Enoxaparin is consistently richer in shorter oligosaccharides than Tinzaparin and Dalteparin. Besides providing the content of terminal groups and individual glucosamine and uronic acid residues with different sulfate substituents, the HSQC-NMR spectra permitted us to evaluate and correlate the content of the pentasaccharide, AT-binding sequence A-G-A*-I-A (AT-bs) through quantification of signals of the disaccharide sequence G-A*.Whereas the percent content of HA species is approximately the same for the three LMWHs, substantial differences were observed for the chain distribution of AT-bs as a function of length, with the AT-bs being preferentially contained in the longest chains of each LMWH. The above information will be useful in establishing structure-activity relationships currently under way. This study is therefore critical for establishing correlations between structural features of LMWHs and their AT-mediated anticoagulant activity.

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Characterization of Low Mololecular Weight Factor VIII.

10.1055/s-0039-1687038 ◽

1979 ◽

Author(s):

G. Rock ◽

D. Palmer ◽

E. Kang ◽

G. Jamieson ◽

W. Cruickshank

Keyword(s):

Molecular Weight ◽

Factor Viii ◽

Polyacrylamide Gel Electrophoresis ◽

Structural Features ◽

Protein Characterization ◽

Low Molecular Weight ◽

Weight Factor ◽

High Molecular Weight Complex ◽

Peptide Map ◽

Polyethylene Glycol Precipitation

The high molecular weight complex of Factor VIII was isolated from resolubilized cryoprecipitate by polyethylene glycol precipitation followed by chromatography on Bio Gel A15M. Upon rechromatography of this compound in buffer containing 1M NaCl and 1mM benzamidine the low molecular weight sub-unit possessing the procoagulant activity eluted at a volume of 2.3V. SDS polyacrylamide gel electrophoresis of this material in 5% acrylamide gave a single band whose Rf indicated a molecular weight of 150,000. The isoelectric point was determined to be 7.4. A peptide map of pepsin digested, I125 labelled material showed very few peptides which were radioactive and/or fluorescamine positive; as well, there was a relatively large amount of radioactive, non-fluorescamine positive material which was slow moving on pH 2.1 electrophoresis and immobile on chromatography. Amino acid analysis yielded data consistent with the presence of a small amount of protein. Carbohydrate analysis indicated a large amount of neutral hexoses, a very small amount of hexosamines and no detectable sialic acid. These results suggest that the structural features of low molecular weight Factor VIII may account for its anomalous behaviour in standard protein characterization procedures.

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Amyloid fibril protein in familial amyloid polyneuropathy

Neurology ◽

10.1212/wnl.31.2.186 ◽

1981 ◽

Vol 31 (2) ◽

pp. 186-186 ◽

Cited By ~ 14

Author(s):

S. Shoji ◽

A. Okano

Keyword(s):

Amyloid Fibril ◽

Familial Amyloid Polyneuropathy ◽

Amyloid Polyneuropathy ◽

Amyloid Fibril Protein

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Steady turnover of amyloid fibril proteins in gastric mucosa after liver transplantation in familial amyloid polyneuropathy

Amyloid ◽

10.3109/13506129.2013.807790 ◽

2013 ◽

Vol 20 (3) ◽

pp. 156-163 ◽

Cited By ~ 6

Author(s):

Ayako Tsuchiya-Suzuki ◽

Masahide Yazaki ◽

Yoshiki Sekijima ◽

Fuyuki Kametani ◽

Shu-ichi Ikeda

Keyword(s):

Liver Transplantation ◽

Gastric Mucosa ◽

Amyloid Fibril ◽

Familial Amyloid Polyneuropathy ◽

Amyloid Polyneuropathy

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Transthyretin Misfolding, A Fatal Structural Pathogenesis Mechanism

International Journal of Molecular Sciences ◽

10.3390/ijms22094429 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4429

Author(s):

Jin-Beom Si ◽

Bokyung Kim ◽

Jin Hae Kim

Keyword(s):

Cerebrospinal Fluid ◽

Thyroid Hormone ◽

Human Plasma ◽

Structural Features ◽

Familial Amyloid Polyneuropathy ◽

Systemic Amyloidosis ◽

Retinol Binding Protein ◽

Senile Systemic Amyloidosis ◽

Amyloid Polyneuropathy ◽

Amyloid Cardiomyopathy

Transthyretin (TTR) is an essential transporter of a thyroid hormone and a holo-retinol binding protein, found abundantly in human plasma and cerebrospinal fluid. In addition, this protein is infamous for its amyloidogenic propensity, causing various amyloidoses in humans, such as senile systemic amyloidosis, familial amyloid polyneuropathy, and familial amyloid cardiomyopathy. It has been known for over two decades that decreased stability of the native tetrameric conformation of TTR is the main cause of these diseases. Yet, mechanistic details on the amyloidogenic transformation of TTR were not clear until recent multidisciplinary investigations on various structural states of TTR. In this review, we discuss recent advancements in the structural understanding of TTR misfolding and amyloidosis processes. Special emphasis has been laid on the observations of novel structural features in various amyloidogenic species of TTR. In addition, proteolysis-induced fragmentation of TTR, a recently proposed mechanism facilitating TTR amyloidosis, has been discussed in light of its structural consequences and relevance to acknowledge the amyloidogenicity of TTR.

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