[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

TitleProfound structural conservation of chemically cross-linked HIV-1 envelope glycoprotein experimental vaccine antigens.
Journal, issue, pagesNPJ Vaccines, Vol. 8, Issue 1, Page 101, Year 2023
Publish dateJul 13, 2023
AuthorsGregory M Martin / Rebecca A Russell / Philip Mundsperger / Scarlett Harris / Lu Jovanoska / Luiza Farache Trajano / Torben Schiffner / Katalin Fabian / Monica Tolazzi / Gabriella Scarlatti / Leon McFarlane / Hannah Cheeseman / Yoann Aldon / Edith E Schermer / Marielle Breemen / Kwinten Sliepen / Dietmar Katinger / Renate Kunert / Rogier W Sanders / Robin Shattock / Andrew B Ward / Quentin J Sattentau /
PubMed AbstractChemical cross-linking is used to stabilize protein structures with additional benefits of pathogen and toxin inactivation for vaccine use, but its use has been restricted by the potential for local ...Chemical cross-linking is used to stabilize protein structures with additional benefits of pathogen and toxin inactivation for vaccine use, but its use has been restricted by the potential for local or global structural distortion. This is of particular importance when the protein in question requires a high degree of structural conservation for inducing a biological outcome such as the elicitation of antibodies to conformationally sensitive epitopes. The HIV-1 envelope glycoprotein (Env) trimer is metastable and shifts between different conformational states, complicating its use as a vaccine antigen. Here we have used the hetero-bifunctional zero-length reagent 1-Ethyl-3-(3-Dimethylaminopropyl)-Carbodiimide (EDC) to cross-link two soluble Env trimers, selected well-folded trimer species using antibody affinity, and transferred this process to good manufacturing practice (GMP) for experimental medicine use. Cross-linking enhanced trimer stability to biophysical and enzyme attack. Cryo-EM analysis revealed that cross-linking retained the overall structure with root-mean-square deviations (RMSDs) between unmodified and cross-linked Env trimers of 0.4-0.5 Å. Despite this negligible distortion of global trimer structure, we identified individual inter-subunit, intra-subunit, and intra-protomer cross-links. Antigenicity and immunogenicity of the trimers were selectively modified by cross-linking, with cross-linked ConS retaining bnAb binding more consistently than ConM. Thus, the EDC cross-linking process improves trimer stability whilst maintaining protein folding, and is readily transferred to GMP, consistent with the more general use of this approach in protein-based vaccine design.
External linksNPJ Vaccines / PubMed:37443366 / PubMed Central
MethodsEM (single particle)
Resolution3.12 - 3.85 Å
Structure data

EMDB-23564, PDB-7lx2:
Cryo-EM structure of ConSOSL.UFO.664 (ConS) in complex with bNAb PGT122
Method: EM (single particle) / Resolution: 3.12 Å

EMDB-23565, PDB-7lx3:
Cryo-EM structure of EDC-crosslinked ConSOSL.UFO.664 (ConS-EDC) in complex with bNAb PGT122
Method: EM (single particle) / Resolution: 3.45 Å

EMDB-23571, PDB-7lxm:
Cryo-EM structure of ConM SOSIP.v7 (ConM) in complex with bNAb PGT122
Method: EM (single particle) / Resolution: 3.41 Å

EMDB-23572, PDB-7lxn:
Cryo-EM structure of EDC-crosslinked ConM SOSIP.v7 (ConM-EDC) in complex with bNAb PGT122
Method: EM (single particle) / Resolution: 3.85 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Env / SOSIP / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex

+
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