2muq
From Proteopedia
Solution Structure of the Human FAAP20 UBZ
Structural highlights
FunctionFAP20_HUMAN Component of the Fanconi anemia (FA) complex required to recruit the FA complex to DNA interstrand cross-links (ICLs) and promote ICLs repair. Following DNA damage recognizes and binds 'Lys-63'-linked ubiquitin generated by RNF8 at ICLs and recruits other components of the FA complex. Promotes translesion synthesis via interaction with REV1.[1] [2] [3] [4] Publication Abstract from PubMedFAAP20 is an integral component of the Fanconi anemia core complex that mediates the repair of DNA interstrand crosslinks. The ubiquitin-binding capacity of the FAAP20 UBZ is required for recruitment of the Fanconi anemia complex to interstrand DNA crosslink sites and for interaction with the translesion synthesis machinery. Although the UBZ-ubiquitin interaction is thought to be exclusively encapsulated within the betabetaalpha module of UBZ, we show that the FAAP20-ubiquitin interaction extends beyond such a canonical zinc-finger motif. Instead, ubiquitin binding by FAAP20 is accompanied by transforming a disordered tail C-terminal to the UBZ of FAAP20 into a rigid, extended beta-loop that latches onto the complex interface of the FAAP20 UBZ and ubiquitin, with the invariant C-terminal tryptophan emanating toward I44Ub for enhanced binding specificity and affinity. Substitution of the C-terminal tryptophan with alanine in FAAP20 not only abolishes FAAP20-ubiquitin binding in vitro, but also causes profound cellular hypersensitivity to DNA interstrand crosslink lesions in vivo, highlighting the indispensable role of the C-terminal tail of FAAP20, beyond the compact zinc finger module, toward ubiquitin recognition and Fanconi anemia complex-mediated DNA interstrand crosslink repair. Ubiquitin recognition by FAAP20 expands the complex interface beyond the canonical UBZ domain.,Wojtaszek JL, Wang S, Kim H, Wu Q, D'Andrea AD, Zhou P Nucleic Acids Res. 2014 Nov 20. pii: gku1153. PMID:25414354[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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