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7ojx

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E2 UBE2K covalently linked to donor Ub, acceptor di-Ub, and RING E3 primed for K48-linked Ub chain synthesis

Structural highlights

7ojx is a 5 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RNF38_HUMAN

Publication Abstract from PubMed

Ubiquitin (Ub) chain types govern distinct biological processes. K48-linked polyUb chains target substrates for proteasomal degradation, but the mechanism of Ub chain synthesis remains elusive due to the transient nature of Ub handover. Here, we present the structure of a chemically trapped complex of the E2 UBE2K covalently linked to donor Ub and acceptor K48-linked di-Ub, primed for K48-linked Ub chain synthesis by a RING E3. The structure reveals the basis for acceptor Ub recognition by UBE2K active site residues and the C-terminal Ub-associated (UBA) domain, to impart K48-linked Ub specificity and catalysis. Furthermore, the structure unveils multiple Ub-binding surfaces on the UBA domain that allow distinct binding modes for K48- and K63-linked Ub chains. This multivalent Ub-binding feature serves to recruit UBE2K to ubiquitinated substrates to overcome weak acceptor Ub affinity and thereby promote chain elongation. These findings elucidate the mechanism of processive K48-linked polyUb chain formation by UBE2K.

Structure of UBE2K-Ub/E3/polyUb reveals mechanisms of K48-linked Ub chain extension.,Nakasone MA, Majorek KA, Gabrielsen M, Sibbet GJ, Smith BO, Huang DT Nat Chem Biol. 2022 Apr;18(4):422-431. doi: 10.1038/s41589-021-00952-x. Epub 2022 , Jan 13. PMID:35027744^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Nakasone MA, Majorek KA, Gabrielsen M, Sibbet GJ, Smith BO, Huang DT. Structure of UBE2K-Ub/E3/polyUb reveals mechanisms of K48-linked Ub chain extension. Nat Chem Biol. 2022 Apr;18(4):422-431. PMID:35027744 doi:10.1038/s41589-021-00952-x