5N38

S65DParkin and pUB complex

Summary for 5N38

• Entry DOI: 10.2210/pdb5n38/pdb
• Descriptor: E3 ubiquitin-protein ligase parkin,E3 ubiquitin-protein ligase parkin, Polyubiquitin-B, DI(HYDROXYETHYL)ETHER, ... (6 entities in total)
• Functional Keywords: s65dparkin pub complex, splicing, ligase
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm, cytosol : O60260; Ubiquitin: Cytoplasm : P0CG47
• Total number of polymer chains: 2
• Total formula weight: 54933.73

Authors

Kumar, A.,Chaugule, V.K.,Johnson, C.,Toth, R.,Sundaramoorthy, R.,Knebel, A.,Walden, H. (deposition date: 2017-02-08, release date: 2017-04-19, Last modification date: 2024-01-17)

Primary citation

Kumar, A.,Chaugule, V.K.,Condos, T.E.C.,Barber, K.R.,Johnson, C.,Toth, R.,Sundaramoorthy, R.,Knebel, A.,Shaw, G.S.,Walden, H.
Parkin-phosphoubiquitin complex reveals cryptic ubiquitin-binding site required for RBR ligase activity.
Nat. Struct. Mol. Biol., 24:475-483, 2017

PubMed Abstract: RING-between-RING (RBR) E3 ligases are a class of ubiquitin ligases distinct from RING or HECT E3 ligases. An important RBR ligase is Parkin, mutations in which lead to early-onset hereditary Parkinsonism. Parkin and other RBR ligases share a catalytic RBR module but are usually autoinhibited and activated via distinct mechanisms. Recent insights into Parkin regulation predict large, unknown conformational changes during Parkin activation. However, current data on active RBR ligases reflect the absence of regulatory domains. Therefore, it remains unclear how individual RBR ligases are activated, and whether they share a common mechanism. We now report the crystal structure of a human Parkin-phosphoubiquitin complex, which shows that phosphoubiquitin binding induces movement in the 'in-between RING' (IBR) domain to reveal a cryptic ubiquitin-binding site. Mutation of this site negatively affects Parkin's activity. Furthermore, ubiquitin binding promotes cooperation between Parkin molecules, which suggests a role for interdomain association in the RBR ligase mechanism.

PubMed: 28414322
DOI: 10.1038/nsmb.3400

Experimental method

X-RAY DIFFRACTION (2.6 Å)