4DRB

The crystal structure of FANCM bound MHF complex

Summary for 4DRB

• Entry DOI: 10.2210/pdb4drb/pdb
• Related: 4DRA
• Descriptor: Centromere protein S, Fanconi anemia group M protein, Centromere protein X, ... (4 entities in total)
• Functional Keywords: dna repair, dna binding complex, histone fold, dna damage repair, dna binding, dna binding-protein binding complex, dna binding protein-protein binding complex, dna binding protein/protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q8N2Z9 Q8IYD8 A8MT69
• Total number of polymer chains: 15
• Total formula weight: 192582.16

Authors

Tao, Y.,Niu, L.,Teng, M. (deposition date: 2012-02-17, release date: 2012-05-16, Last modification date: 2024-10-16)

Primary citation

Tao, Y.,Jin, C.,Li, X.,Qi, S.,Chu, L.,Niu, L.,Yao, X.,Teng, M.
The structure of the FANCM-MHF complex reveals physical features for functional assembly
Nat Commun, 3:782-782, 2012

PubMed 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.

PubMed: 22510687
DOI: 10.1038/ncomms1779

Experimental method

X-RAY DIFFRACTION (2.634 Å)