4DRB: The Crystal Structure Of Fancm Bound Mhf Complex

Citation:
Abstract
Fanconi anaemia is a rare genetic disease characterized by chromosomal instability and cancer susceptibility. The Fanconi anaemia complementation group protein M (FANCM) forms an evolutionarily conserved DNA-processing complex with MHF1/MHF2 (histone-fold-containing proteins), which is essential for DNA repair in response to genotoxic stress. Here we present the crystal structures of the MHF1-MHF2 complex alone and bound to a fragment of FANCM (FANCM(661-800), designated FANCM-F). The structures show that MHF1 and MHF2 form a compact tetramer to which FANCM-F binds through a 'dual-V' shaped structure. FANCM-F and (MHF1-MHF2)(2) cooperate to constitute a new DNA-binding site that is coupled to the canonical L1L2 region. Perturbation of the MHF-FANCM-F structural plasticity changes the localization of FANCM in vivo. The MHF-FANCM interaction and its subcellular localization are altered by a disease-associated mutant of FANCM. These findings reveal the molecular basis of MHF-FANCM recognition and provide mechanistic insights into the pathway leading to Fanconi anaemia.
PDB ID: 4DRBDownload
MMDB ID: 99726
PDB Deposition Date: 2012/2/17
Updated in MMDB: 2012/05
Experimental Method:
x-ray diffraction
Resolution: 2.63  Å
Source Organism:
Similar Structures:
Biological Unit for 4DRB: pentameric; determined by author and by software (PISA)
Molecular Components in 4DRB
Label Count Molecule
Proteins (5 molecules)
2
Centromere Protein S(Gene symbol: CENPS)
Molecule annotation
1
Fanconi Anemia Group M Protein(Gene symbol: FANCM)
Molecule annotation
2
Centromere Protein X(Gene symbol: CENPX)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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