[English] 日本語
Yorodumi Papers
- Database of articles cited by EMDB/PDB/SASBDB data -

+
Search query

Keywords
Structure methods
Author
Journal
IF

-
Structure paper

TitleContinuous evolution of compact protein degradation tags regulated by selective molecular glues.
Journal, issue, pagesScience, Vol. 383, Issue 6688, Page eadk4422, Year 2024
Publish dateMar 15, 2024
AuthorsJaron A M Mercer / Stephan J DeCarlo / Shourya S Roy Burman / Vedagopuram Sreekanth / Andrew T Nelson / Moritz Hunkeler / Peter J Chen / Katherine A Donovan / Praveen Kokkonda / Praveen K Tiwari / Veronika M Shoba / Arghya Deb / Amit Choudhary / Eric S Fischer / David R Liu /
PubMed AbstractConditional protein degradation tags (degrons) are usually >100 amino acids long or are triggered by small molecules with substantial off-target effects, thwarting their use as specific modulators of ...Conditional protein degradation tags (degrons) are usually >100 amino acids long or are triggered by small molecules with substantial off-target effects, thwarting their use as specific modulators of endogenous protein levels. We developed a phage-assisted continuous evolution platform for molecular glue complexes (MG-PACE) and evolved a 36-amino acid zinc finger (ZF) degron (SD40) that binds the ubiquitin ligase substrate receptor cereblon in complex with PT-179, an orthogonal thalidomide derivative. Endogenous proteins tagged in-frame with SD40 using prime editing are degraded by otherwise inert PT-179. Cryo-electron microscopy structures of SD40 in complex with ligand-bound cereblon revealed mechanistic insights into the molecular basis of SD40's activity and specificity. Our efforts establish a system for continuous evolution of molecular glue complexes and provide ZF tags that overcome shortcomings associated with existing degrons.
External linksScience / PubMed:38484051
MethodsEM (single particle)
Resolution2.41 - 3.37 Å
Structure data

41423

8tnp

EMDB-41423, PDB-8tnp:
Cryo-EM structure of DDB1dB:CRBN:Pomalidomide:SD40
Method: EM (single particle) / Resolution: 3.3 Å

41424

8tnq

EMDB-41424, PDB-8tnq:
Cryo-EM structure of DDB1dB:CRBN:PT-179:SD40, conformation 1
Method: EM (single particle) / Resolution: 2.41 Å

41425

8tnr

EMDB-41425, PDB-8tnr:
Cryo-EM structure of DDB1dB:CRBN:PT-179:SD40, conformation 2
Method: EM (single particle) / Resolution: 2.5 Å

EMDB-41777: Map from local refinement (focused on CRBN) of DDB1dB:CRBN:Pomalidomide:SD40
Method: EM (single particle) / Resolution: 3.37 Å

EMDB-41778: Map from local refinement (focused on CRBN) of DDB1dB:CRBN:PT-179:SD40, conformation 1
Method: EM (single particle) / Resolution: 2.55 Å

EMDB-41779: Map from local refinement (focused on CRBN) of DDB1dB:CRBN:PT-179:SD40, conformation 2
Method: EM (single particle) / Resolution: 2.72 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-Y70:
S-Pomalidomide


ChemComp, No image

ChemComp-MIQ:
Unknown entry

Source
  • homo sapiens (human)
  • escherichia coli (E. coli)
KeywordsTRANSFERASE / ubiquitin / CRBN / directed evolution / Zinc finger / IMiD / Molecular Glue

+
About Yorodumi Papers

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi Papers

Database of articles cited by EMDB/PDB/SASBDB data

  • Database of articles cited by EMDB, PDB, and SASBDB entries
  • Using PubMed data

Related info.:EMDB / PDB / SASBDB / Yorodumi / EMN Papers / Changes in new EM Navigator and Yorodumi

Read more