[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

TitleStructure-based design of non-hypertrophic apelin receptor modulator.
Journal, issue, pagesCell, Vol. 187, Issue 6, Page 1460-1475.e20, Year 2024
Publish dateMar 14, 2024
AuthorsWei-Wei Wang / Su-Yu Ji / Wenjia Zhang / Junxia Zhang / Chenxi Cai / Rubi Hu / Shao-Kun Zang / Luwei Miao / Haomang Xu / Li-Nan Chen / Zongkuai Yang / Jia Guo / Jiao Qin / Dan-Dan Shen / Ping Liang / Yan Zhang / Yan Zhang /
PubMed AbstractApelin is a key hormone in cardiovascular homeostasis that activates the apelin receptor (APLNR), which is regarded as a promising therapeutic target for cardiovascular disease. However, adverse ...Apelin is a key hormone in cardiovascular homeostasis that activates the apelin receptor (APLNR), which is regarded as a promising therapeutic target for cardiovascular disease. However, adverse effects through the β-arrestin pathway limit its pharmacological use. Here, we report cryoelectron microscopy (cryo-EM) structures of APLNR-G complexes bound to three agonists with divergent signaling profiles. Combined with functional assays, we have identified "twin hotspots" in APLNR as key determinants for signaling bias, guiding the rational design of two exclusive G-protein-biased agonists WN353 and WN561. Cryo-EM structures of WN353- and WN561-stimulated APLNR-G protein complexes further confirm that the designed ligands adopt the desired poses. Pathophysiological experiments have provided evidence that WN561 demonstrates superior therapeutic effects against cardiac hypertrophy and reduced adverse effects compared with the established APLNR agonists. In summary, our designed APLNR modulator may facilitate the development of next-generation cardiovascular medications.
External linksCell / PubMed:38428423
MethodsEM (single particle)
Resolution2.4 - 3.2 Å
Structure data

38794

8xzf

EMDB-38794, PDB-8xzf:
Cryo-EM structure of the WN561-bound human APLNR-Gi complex
Method: EM (single particle) / Resolution: 3.0 Å

38795

8xzg

EMDB-38795, PDB-8xzg:
Cryo-EM structure of the [Pyr1]-apelin-13-bound human APLNR-Gi complex
Method: EM (single particle) / Resolution: 3.2 Å

38796

8xzh

EMDB-38796, PDB-8xzh:
Cryo-EM structure of the MM07-bound human APLNR-Gi complex
Method: EM (single particle) / Resolution: 2.6 Å

38797

8xzi

EMDB-38797, PDB-8xzi:
Cryo-EM structure of the CMF-019-bound human APLNR-Gi complex
Method: EM (single particle) / Resolution: 2.7 Å

38798

8xzj

EMDB-38798, PDB-8xzj:
Cryo-EM structure of the WN353-bound human APLNR-Gi complex
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-38967: The focused refinement map (Receptor) of the MM07 bound APLNR-Gi1 structure.
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-38969: The focused refinement map (G-protein) of MM07 bound APLNR-Gi1 structure.
Method: EM (single particle) / Resolution: 2.4 Å

EMDB-38970: The low resolution consensus map of the MM07 bound APLNR-Gi1 structure.
Method: EM (single particle) / Resolution: 2.5 Å

EMDB-38971: The focused refinement map (Receptor) of CMF-019 bound APLNR-Gi1 structure.
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-38972: The focused refinement map (G-protein) of CMF-019 bound APLNR-Gi1 structure.
Method: EM (single particle) / Resolution: 2.5 Å

EMDB-38973: CMF-019 bound APLNR complex
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-38974: The focused refinement map (Receptor) of WN353 bound APLNR-Gi1 structure
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-38975: The focused refinement map (G-protein) of WN353 bound APLNR-Gi1 structure
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-38976: WN353 bound APLNR complex
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-38977: The focused refinement map (Receptor) of WN561 bound APLNR-Gi1 structure.
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-38978: The focused refinement map (G-protein) of WN561 bound APLNR-Gi1 structure
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-38979: WN561 bound APLNR complex
Method: EM (single particle) / Resolution: 2.9 Å

Chemicals

PDB-1d5n:
CRYSTAL STRUCTURE OF E. COLI MNSOD AT 100K

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsMEMBRANE PROTEIN / APLNR / Class A GPCR / Synthetic peptide / apelin / Structural protein / MM07 / Cyclic peptide / CMF-019 / G-protein-biased small molecule agonist

+
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