Amyloid Core Wild-Type Apomyoglobin and Its Mutant Variants Is Formed by Different Regions of the Polypeptide Chain

被引：0

作者：

Katina, N. S. ^{[1
]}

Grigorashvili, E. I. ^{[1
]}

Suvorina, M. Yu. ^{[1
]}

Ilyina, N. B. ^{[1
]}

Ryabova, N. A. ^{[1
]}

Selivanova, O. M. ^{[1
]}

Surin, A. K. ^{[1
]}

机构：

[1] Russian Acad Sci, Inst Prot Res, Pushchino 142290, Moscow Oblast, Russia

来源：

MOLECULAR BIOLOGY | 2018年 / 52卷 / 01期

基金：

俄罗斯科学基金会;

关键词：

amyloids; apomyoglobin; limited proteolysis; polymorphism of amyloids; mass spectrometry; SOLID-STATE NMR; REVEALS STRUCTURAL DIFFERENCES; LIMITED PROTEOLYSIS; ALZHEIMERS-DISEASE; FIBRIL FORMATION; ALPHA-SYNUCLEIN; A-BETA; AGGREGATE CYTOTOXICITY; PROTEIN AGGREGATION; POLYMORPHISM;

D O I：

10.1134/S0026893318010089

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

As has been recently shown, the toxicity of protein aggregates is determined by their structure. Therefore, special attention has been focused on the search for factors that specify the structural features of formed amyloid fibrils. The effect of amino acid substitutions in apomyoglobin on the structural characteristics of its amyloid aggregates has been analyzed. The morphology and secondary structure of amyloids of the wild-type protein and its mutant variants Val10Ala, Val10Phe, and Trp14Phe have been compared, and the regions involved in intermolecular interactions in fibrils have been determined using limited proteolysis and mass spectrometry. No considerable differences have been found in the morphology (shape, length, or diameter) or the content (percentage) of the cross-beta structure of apomyoglobin amyloids and its mutant variants. Amyloid cores of wild-type apomyoglobin and variants with Val10Phe and Trp14Phe substitutions have been formed by different regions of the polypeptide chain. The case study of apomyoglobin demonstrates that the location of amyloidogenic regions in the polypeptide chain of wild-type protein and its mutant forms can differ. Thus, possible structural changes in amyloids resulting from amino acid substitutions should be taken into account when studying phenotype aggregation.

引用

页码：42 / 51

页数：10

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