Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Profound structural conservation of chemically cross-linked HIV-1 envelope glycoprotein experimental vaccine antigens.
Journal, issue, pages	NPJ Vaccines, Vol. 8, Issue 1, Page 101, Year 2023
Publish date	Jul 13, 2023
Authors	Gregory 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 Abstract	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 ...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 links	NPJ Vaccines / PubMed:37443366 / PubMed Central
Methods	EM (single particle)
Resolution	3.12 - 3.85 Å
Structure data	23564 7lx2 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 23565 7lx3 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 23571 7lxm 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 23572 7lxn 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)
Keywords	VIRAL PROTEIN/IMMUNE SYSTEM / Env / SOSIP / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex