6do4

KLHDC2 ubiquitin ligase in complex with SelS C-end degron

spinqualitylabelsall models 6do4, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6do4 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: KLHDC2, HCA33 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [KLDC2_HUMAN] Represses CREB3-mediated transcription by interfering with CREB3-DNA binding. Publication Abstract from PubMed Aberrant proteins can be deleterious to cells and are cleared by the ubiquitin-proteasome system. A group of C-end degrons that are recognized by specific cullin-RING ubiquitin E3 ligases (CRLs) has recently been identified in some of these abnormal polypeptides. Here, we report three crystal structures of a CRL2 substrate receptor, KLHDC2, in complex with the diglycine-ending C-end degrons of two early-terminated selenoproteins and the N-terminal proteolytic fragment of USP1. The E3 recognizes the degron peptides in a similarly coiled conformation and cradles their C-terminal diglycine with a deep surface pocket. By hydrogen bonding with multiple backbone carbonyls of the peptides, KLHDC2 further locks in the otherwise degenerate degrons with a compact interface and unexpected high affinities. Our results reveal the structural mechanism by which KLHDC2 recognizes the simplest C-end degron and suggest a functional necessity of the E3 to tightly maintain the low abundance of its select substrates. Recognition of the Diglycine C-End Degron by CRL2(KLHDC2) Ubiquitin Ligase.,Rusnac DV, Lin HC, Canzani D, Tien KX, Hinds TR, Tsue AF, Bush MF, Yen HS, Zheng N Mol Cell. 2018 Dec 6;72(5):813-822.e4. doi: 10.1016/j.molcel.2018.10.021. PMID:30526872 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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