5YMY

The structure of the complex between Rpn13 and K48-diUb

Summary for 5YMY

• Entry DOI: 10.2210/pdb5ymy/pdb
• Descriptor: Ubiquitin, Proteasomal ubiquitin receptor ADRM1 (3 entities in total)
• Functional Keywords: complex, ubiquitin receptor, compacted, protein binding-signaling protein complex, protein binding/signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 33923.72

Authors

Liu, Z.,Dong, X.,Gong, Z.,Yi, H.W.,Liu, K.,Yang, J.,Zhang, W.P.,Tang, C. (deposition date: 2017-10-22, release date: 2019-03-13, Last modification date: 2024-11-13)

Primary citation

Liu, Z.,Dong, X.,Yi, H.W.,Yang, J.,Gong, Z.,Wang, Y.,Liu, K.,Zhang, W.P.,Tang, C.
Structural basis for the recognition of K48-linked Ub chain by proteasomal receptor Rpn13.
Cell Discov, 5:19-19, 2019

PubMed Abstract: The interaction between K48-linked ubiquitin (Ub) chain and Rpn13 is important for proteasomal degradation of ubiquitinated substrate proteins. Only the complex structure between the N-terminal domain of Rpn13 (Rpn13) and Ub monomer has been characterized, while it remains unclear how Rpn13 specifically recognizes K48-linked Ub chain. Using single-molecule FRET, here we show that K48-linked diubiquitin (K48-diUb) fluctuates among distinct conformational states, and a preexisting compact state is selectively enriched by Rpn13. The same binding mode is observed for full-length Rpn13 and longer K48-linked Ub chain. Using solution NMR spectroscopy, we have determined the complex structure between Rpn13 and K48-diUb. In this structure, Rpn13 simultaneously interacts with proximal and distal Ub subunits of K48-diUb that remain associated in the complex, thus corroborating smFRET findings. The proximal Ub interacts with Rpn13 similarly as the Ub monomer in the known Rpn13:Ub structure, while the distal Ub binds to a largely electrostatic surface of Rpn13. Thus, a charge-reversal mutation in Rpn13 weakens the interaction between Rpn13 and K48-linked Ub chain, causing accumulation of ubiquitinated proteins. Moreover, physical blockage of the access of the distal Ub to Rpn13 with a proximity-attached Ub monomer can disrupt the interaction between Rpn13 and K48-diUb. Taken together, the bivalent interaction of K48-linked Ub chain with Rpn13 provides the structural basis for Rpn13 linkage selectivity, which opens a new window for modulating proteasomal function.

PubMed: 30962947
DOI: 10.1038/s41421-019-0089-7

Experimental method

SOLUTION NMR