Structural analysis of a replication protein encoded by a plasmid isolated from a multiple sclerosis patient

Acta Crystallogr D Struct Biol. 2019 May 1;75(Pt 5):498-504. doi: 10.1107/S2059798319003991. Epub 2019 Apr 29.


Bovine meat and milk factors (BMMFs) are circular, single-stranded episomal DNAs that have been detected in bovine meat and milk products. BMMFs are thought to have roles in human malignant and degenerative diseases. BMMFs encode a replication initiator protein (Rep) that is actively transcribed and translated in human cells. In this study, a Rep WH1 domain encoded on a BMMF (MSBI1.176) isolated from a multiple sclerosis human brain sample was determined to 1.53 Å resolution using X-ray crystallography. The overall structure of the MSBI1.176 WH1 domain was remarkably similar to other Rep structures, despite having a low (28%) amino-acid sequence identity. The MSBI1.176 WH1 domain contained elements common to other Reps, including five α-helices, five β-strands and a hydrophobic pocket. These new findings suggest that the MSBI1.176 Rep might have comparable roles and functions to other known Reps of different origins.

Keywords: X-ray crystal structure; bovine meat and milk factors; episomal circular DNA; multiple sclerosis; trans-acting replication initiator protein.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / metabolism*
  • Cattle
  • Crystallography, X-Ray
  • DNA Helicases / chemistry*
  • DNA Helicases / metabolism*
  • Humans
  • Models, Molecular
  • Multiple Sclerosis / metabolism*
  • Plasmids / isolation & purification*
  • Plasmids / metabolism*
  • Protein Binding
  • Protein Conformation
  • Protein Domains
  • Sequence Homology
  • Trans-Activators / chemistry*
  • Trans-Activators / metabolism*


  • Trans-Activators
  • replication initiator protein
  • DNA Helicases