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

Int J Mol Sci. 2021 Jan 13;22(2):731. doi: 10.3390/ijms22020731.


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.

Keywords: CD; DLS; MyBP-C; SAXS; X-ray diffraction; amyloid; amyloid-like aggregation; muscle proteins; protein aggregation; structural analysis.

MeSH terms

  • Amino Acid Sequence
  • Amyloid / chemistry*
  • Amyloid / metabolism*
  • Amyloid / ultrastructure
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Chromatography, High Pressure Liquid
  • Circular Dichroism
  • Dynamic Light Scattering
  • In Vitro Techniques
  • Kinetics
  • Mass Spectrometry
  • Models, Molecular
  • Protein Aggregates*
  • Protein Aggregation, Pathological
  • Protein Conformation
  • Structure-Activity Relationship
  • X-Ray Diffraction


  • Amyloid
  • Carrier Proteins
  • Protein Aggregates
  • myosin-binding protein C