Structural peculiarities of the (MHF1-MHF2)4 octamer provide a long DNA binding patch to anchor the MHF-FANCM complex to chromatin: a solution SAXS study

FEBS Lett. 2013 Sep 17;587(18):2912-7. doi: 10.1016/j.febslet.2013.07.022. Epub 2013 Jul 22.

Abstract

MHF1 and MHF2 are histone-fold-containing FANCM-associated proteins. FANCM is a Fanconi anemia (FA) complementation group protein. We previously obtained high-resolution structures of MHF1-MHF2 (MHF) and MHF in complex with a fragment of FANCM (MHF-FANCM-F). Here, we use small angle X-ray scattering (SAXS) to investigate the solution behaviors of these protein complexes. In combination with crystallographic data, the results of the SAXS study reveal that a long, positively charged patch exposed on the surface of the MHF complex plays a critical role in double-stranded DNA (dsDNA) binding.

Keywords: DNA binding patch; FA; FANCM; Fanconi anaemia; Fanconi anemia; ICLs; MHF; MHF complex; MHF in complex with a fragment of FANCM; MHF1–MHF2; MHF–FANCM-F; MM; SAXS; SEC; double strand DNA; dsDNA; interstrand crosslinks; molecular mass; size-exclusion chromatography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / chemistry*
  • Apoptosis Regulatory Proteins / genetics
  • Binding Sites
  • Chromatin / chemistry*
  • Chromatin / genetics
  • DNA / chemistry*
  • DNA / genetics
  • DNA Helicases / chemistry*
  • DNA Helicases / genetics
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • Gene Expression
  • Humans
  • Models, Molecular*
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / genetics
  • Protein Binding
  • Protein Multimerization
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Scattering, Small Angle
  • Solutions
  • Static Electricity
  • Tumor Suppressor Proteins / chemistry*
  • Tumor Suppressor Proteins / genetics
  • X-Ray Diffraction

Substances

  • Apoptosis Regulatory Proteins
  • CENPS protein, human
  • CENPX protein, human
  • Chromatin
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Recombinant Proteins
  • Solutions
  • Tumor Suppressor Proteins
  • DNA
  • FANCM protein, human
  • DNA Helicases