8c3h
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex a long aspartimide degron peptide== | |
| + | <StructureSection load='8c3h' size='340' side='right'caption='[[8c3h]], [[Resolution|resolution]] 1.71Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8c3h]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Magnetospirillum_gryphiswaldense Magnetospirillum gryphiswaldense]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8C3H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8C3H FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SNN:L-3-AMINOSUCCINIMIDE'>SNN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8c3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8c3h OCA], [https://pdbe.org/8c3h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8c3h RCSB], [https://www.ebi.ac.uk/pdbsum/8c3h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8c3h ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/A4TVL0_9PROT A4TVL0_9PROT] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:36701892</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8c3h" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Magnetospirillum gryphiswaldense]] | ||
| + | [[Category: Hartmann MD]] | ||
| + | [[Category: Heim C]] | ||
| + | [[Category: Spring AK]] | ||
Revision as of 06:46, 8 February 2023
Cereblon isoform 4 from Magnetospirillum gryphiswaldense in complex a long aspartimide degron peptide
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