8c3h

Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex a long aspartimide degron peptide

spinqualitylabelsall models 8c3h, resolution 1.71Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8c3h is a 5 chain structure with sequence from Homo sapiens and Magnetospirillum gryphiswaldense. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.71Å Ligands: SNN, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A4TVL0_9PROT Publication Abstract from PubMed In targeted protein degradation, immunomodulatory drugs (IMiDs) or cereblon (CRBN) E3 ligase modulatory drugs (CELMoDs) recruit neo-substrate proteins to the E3 ubiquitin ligase receptor CRBN for ubiquitination and subsequent proteasomal degradation. While the structural basis of this mechanism is generally understood, we have only recently described the recognition mode of the natural CRBN degron. In this communication, we reveal that the IMiD- or CELMoD-mediated binding of neo-substrates closely mimics the recognition of natural degrons. In crystal structures, we identify a conserved binding mode for natural degron peptides with an elaborate hydrogen bonding network involving the backbone of each of the six C-terminal degron residues, without the involvement of side chains. In a structural comparison, we show that neo-substrates recruited by IMiDs or CELMoDs emulate every single hydrogen bond of this network and thereby explain the origins of the largely sequence-independent recognition of neo-substrates. Our results imply that the V388I substitution in CRBN does not impair natural degron recognition and complete the structural basis for the rational design of CRBN effectors. Cereblon neo-substrate binding mimics the recognition of the cyclic imide degron.,Heim C, Spring AK, Kirchgassner S, Schwarzer D, Hartmann MD Biochem Biophys Res Commun. 2023 Feb 26;646:30-35. doi: , 10.1016/j.bbrc.2023.01.051. Epub 2023 Jan 18. PMID:36701892 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA