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PDBsum entry 5e6j
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References listed in PDB file
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Key reference
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Title
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Recognition of lys48-Linked di-Ubiquitin and deubiquitinating activities of the sars coronavirus papain-Like protease.
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Authors
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M.Békés,
G.J.Van der heden van noort,
R.Ekkebus,
H.Ovaa,
T.T.Huang,
C.D.Lima.
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Ref.
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Mol Cell, 2016,
62,
572-585.
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PubMed id
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Abstract
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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.
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