2MUR

Solution Structure of the Human FAAP20 UBZ-Ubiquitin Complex

Summary for 2MUR

• Entry DOI: 10.2210/pdb2mur/pdb
• Related: 2MUQ
• NMR Information: BMRB: 25230
• Descriptor: Fanconi anemia-associated protein of 20 kDa, Ubiquitin, ZINC ION (3 entities in total)
• Functional Keywords: ubz, faap20, zinc-finger, fanconi anemia, protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q6NZ36; Ubiquitin: Cytoplasm . 60S ribosomal protein L40: Cytoplasm : P62987
• Total number of polymer chains: 2
• Total formula weight: 13720.96

Authors

Wang, S.,Wojtaszek, J.L.,Zhou, P. (deposition date: 2014-09-16, release date: 2014-12-03, Last modification date: 2024-05-15)

Primary citation

Wojtaszek, J.L.,Wang, S.,Kim, H.,Wu, Q.,D'Andrea, A.D.,Zhou, P.
Ubiquitin recognition by FAAP20 expands the complex interface beyond the canonical UBZ domain.
Nucleic Acids Res., 42:13997-14005, 2014

PubMed Abstract: FAAP20 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 ββα 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 β-loop that latches onto the complex interface of the FAAP20 UBZ and ubiquitin, with the invariant C-terminal tryptophan emanating toward I44(Ub) 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.

PubMed: 25414354
DOI: 10.1093/nar/gku1153

Experimental method

SOLUTION NMR