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Myosin Binding Protein-C Forms Amyloid-Like Aggregates In Vitro.

Liya G BobylevaSergey A ShumeykoElmira I YakupovaAlexey K SurinOxana V GalzitskayaHiroshi KiharaAlexander A TimchenkoMaria A TimchenkoNikita V PenkovAlexey D NikulinMariya Yu SuvorinaNikolay V MolochkovMikhail Yu LobanovRoman S FadeevIvan M VikhlyantsevAlexander G Bobylev
Published in: International journal of molecular sciences (2021)
This work investigated in vitro aggregation and amyloid properties of skeletal myosin binding protein-C (sMyBP-C) interacting in vivo with proteins of thick and thin filaments in the sarcomeric A-disc. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) found a rapid (5-10 min) formation of large (>2 μm) aggregates. sMyBP-C oligomers formed both at the initial 5-10 min and after 16 h of aggregation. Small angle X-ray scattering (SAXS) and DLS revealed sMyBP-C oligomers to consist of 7-10 monomers. TEM and atomic force microscopy (AFM) showed sMyBP-C to form amorphous aggregates (and, to a lesser degree, fibrillar structures) exhibiting no toxicity on cell culture. X-ray diffraction of sMyBP-C aggregates registered reflections attributed to a cross-β quaternary structure. Circular dichroism (CD) showed the formation of the amyloid-like structure to occur without changes in the sMyBP-C secondary structure. The obtained results indicating a high in vitro aggregability of sMyBP-C are, apparently, a consequence of structural features of the domain organization of proteins of this family. Formation of pathological amyloid or amyloid-like sMyBP-C aggregates in vivo is little probable due to amino-acid sequence low identity (<26%), alternating ordered/disordered regions in the protein molecule, and S-S bonds providing for general stability.
Keyphrases
  • binding protein
  • atomic force microscopy
  • electron microscopy
  • high resolution
  • amino acid
  • high speed
  • single molecule
  • oxidative stress
  • single cell
  • protein protein
  • sensitive detection