5E6J

Structure of SARS PLpro bound to a Lys48-linked di-ubiquitin activity based probe

Summary for 5E6J

• Entry DOI: 10.2210/pdb5e6j/pdb
• Descriptor: Replicase polyprotein 1ab, ubiquitin, Polyubiquitin-B, ... (6 entities in total)
• Functional Keywords: sars plpro, deubiquitinating enzyme, ubiquitin, activity based probe, k48-linkage, hydrolase
• Biological source: Human SARS coronavirus (SARS-CoV); More
• Total number of polymer chains: 6
• Total formula weight: 107784.14

Authors

Lima, C.D.,Bekes, M. (deposition date: 2015-10-09, release date: 2016-05-18, Last modification date: 2023-11-15)

Primary citation

Bekes, M.,van der Heden van Noort, G.J.,Ekkebus, R.,Ovaa, H.,Huang, T.T.,Lima, C.D.
Recognition of Lys48-Linked Di-ubiquitin and Deubiquitinating Activities of the SARS Coronavirus Papain-like Protease.
Mol. Cell, 62:572-585, 2016

PubMed Abstract: Deubiquitinating enzymes (DUBs) recognize and cleave linkage-specific polyubiquitin (polyUb) chains, but mechanisms underlying specificity remain elusive in many cases. The severe acute respiratory syndrome (SARS) coronavirus papain-like protease (PLpro) is a DUB that cleaves ISG15, a two-domain Ub-like protein, and Lys48-linked polyUb chains, releasing diUb(Lys48) products. To elucidate this specificity, we report the 2.85 Å crystal structure of SARS PLpro bound to a diUb(Lys48) activity-based probe. SARS PLpro binds diUb(Lys48) in an extended conformation via two contact sites, S1 and S2, which are proximal and distal to the active site, respectively. We show that specificity for polyUb(Lys48) chains is predicated on contacts in the S2 site and enhanced by an S1-S1' preference for a Lys48 linkage across the active site. In contrast, ISG15 specificity is dominated by contacts in the S1 site. Determinants revealed for polyUb(Lys48) specificity should prove useful in understanding PLpro deubiquitinating activities in coronavirus infections.

PubMed: 27203180
DOI: 10.1016/j.molcel.2016.04.016

Experimental method

X-RAY DIFFRACTION (2.85 Å)