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PDBsum entry 2nbv
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Protein binding
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PDB id
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2nbv
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References listed in PDB file
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Key reference
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Title
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Structures of rpn1 t1:rad23 and hrpn13:hplic2 reveal distinct binding mechanisms between substrate receptors and shuttle factors of the proteasome.
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Authors
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X.Chen,
L.Randles,
K.Shi,
S.G.Tarasov,
H.Aihara,
K.J.Walters.
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Ref.
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Structure, 2016,
24,
1257-1270.
[DOI no: ]
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PubMed id
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Abstract
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Three receptors (Rpn1/S2/PSMD2, Rpn10/S5a, Rpn13/Adrm1) in the proteasome bind
substrates by interacting with conjugated ubiquitin chains and/or shuttle
factors (Rad23/HR23, Dsk2/PLIC/ubiquilin, Ddi1) that carry ubiquitinated
substrates to proteasomes. We solved the structure of two such receptors with
their preferred shuttle factor, namely hRpn13(Pru):hPLIC2(UBL) and scRpn1
T1:scRad23(UBL). We find that ubiquitin folds in Rad23 and Dsk2 are fine-tuned
by residue substitutions to achieve high affinity for Rpn1 and Rpn13,
respectively. A single substitution in hPLIC2 yields enhanced interactions with
the Rpn13 ubiquitin contact surface and sterically blocks hRpn13 binding to its
preferred ubiquitin chain type, K48-linked chains. Rpn1 T1 binds two ubiquitins
in tandem and we find that Rad23 binds exclusively to the higher-affinity
Helix28/Helix30 site. Rad23 contacts at Helix28/Helix30 are optimized compared
to ubiquitin by multiple conservative amino acid substitutions. Thus, shuttle
factors deliver substrates to proteasomes through fine-tuned ubiquitin-like
surfaces.
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