4BXO

Architecture and DNA recognition elements of the Fanconi anemia FANCM- FAAP24 complex

Summary for 4BXO

• Entry DOI: 10.2210/pdb4bxo/pdb
• Descriptor: FANCONI ANEMIA GROUP M PROTEIN, FANCONI ANEMIA-ASSOCIATED PROTEIN OF 24 KDA, 5'-D(*TP*CP*AP*GP*CP*AP*TP*CP*AP*TP*CP)-3', ... (6 entities in total)
• Functional Keywords: hydrolase-dna complex, dna binding, pseudo-nuclease, hydrolase/dna
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus : Q8IYD8 Q9BTP7
• Total number of polymer chains: 4
• Total formula weight: 59689.65

Authors

Coulthard, R.,Deans, A.,Swuec, P.,Bowles, M.,Purkiss, A.,Costa, A.,West, S.,McDonald, N. (deposition date: 2013-07-15, release date: 2013-08-28, Last modification date: 2024-05-08)

Primary citation

Coulthard, R.,Deans, A.J.,Swuec, P.,Bowles, M.,Costa, A.,West, S.C.,Mcdonald, N.Q.
Architecture and DNA Recognition Elements of the Fanconi Anemia Fancm-Faap24 Complex.
Structure, 21:1648-, 2013

PubMed Abstract: Fanconi anemia (FA) is a disorder associated with a failure in DNA repair. FANCM (defective in FA complementation group M) and its partner FAAP24 target other FA proteins to sites of DNA damage. FANCM-FAAP24 is related to XPF/MUS81 endonucleases but lacks endonucleolytic activity. We report a structure of an FANCM C-terminal fragment (FANCMCTD) bound to FAAP24 and DNA. This S-shaped structure reveals the FANCM (HhH)2 domain is buried, whereas the FAAP24 (HhH)2 domain engages DNA. We identify a second DNA contact and a metal center within the FANCM pseudo-nuclease domain and demonstrate that mutations in either region impair double-stranded DNA binding in vitro and FANCM-FAAP24 function in vivo. We show the FANCM translocase domain lies in proximity to FANCMCTD by electron microscopy and that binding fork DNA structures stimulate its ATPase activity. This suggests a tracking model for FANCM-FAAP24 until an encounter with a stalled replication fork triggers ATPase-mediated fork remodeling.

PubMed: 23932590
DOI: 10.1016/J.STR.2013.07.006

Experimental method

X-RAY DIFFRACTION (2.15 Å)