6P8N

Crystal Structure of Antibody P-p1f1 in Complex with eOD-GT8

Summary for 6P8N

• Entry DOI: 10.2210/pdb6p8n/pdb
• Descriptor: Env outer domain eOD-GT8, P-p1f1 Heavy Chain, P-p1f1 Light Chain, ... (7 entities in total)
• Functional Keywords: antibody, immunization, immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 6
• Total formula weight: 137025.56

Authors

Weidle, C.,Pancera, M. (deposition date: 2019-06-07, release date: 2019-11-20, Last modification date: 2024-10-23)

Primary citation

Parks, K.R.,MacCamy, A.J.,Trichka, J.,Gray, M.,Weidle, C.,Borst, A.J.,Khechaduri, A.,Takushi, B.,Agrawal, P.,Guenaga, J.,Wyatt, R.T.,Coler, R.,Seaman, M.,LaBranche, C.,Montefiori, D.C.,Veesler, D.,Pancera, M.,McGuire, A.,Stamatatos, L.
Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization.
Cell Rep, 29:3060-3072.e7, 2019

PubMed Abstract: Broadly HIV-1 neutralizing VRC01 class antibodies target the CD4-binding site of Env. They are derived from VH1-202 antibody heavy chains paired with rare light chains expressing 5-amino acid-long CDRL3s. They have been isolated from infected subjects but have not yet been elicited by immunization. Env-derived immunogens capable of binding the germline forms of VRC01 B cell receptors on naive B cells have been designed and evaluated in knockin mice. However, the elicited antibodies cannot bypass glycans present on the conserved position N276 of Env, which restricts access to the CD4-binding site. Efforts to guide the appropriate maturation of these antibodies by sequential immunization have not yet been successful. Here, we report on a two-step immunization scheme that leads to the maturation of VRC01-like antibodies capable of accommodating the N276 glycan and displaying autologous tier 2 neutralizing activities. Our results are relevant to clinical trials aiming to elicit VRC01 antibodies.

PubMed: 31801073
DOI: 10.1016/j.celrep.2019.10.071

Experimental method

X-RAY DIFFRACTION (3.202 Å)