9BDI
Crystal structure of HIV-1 MPER scaffold in complex with antibody Fab Ab45.2
Summary for 9BDI
| Entry DOI | 10.2210/pdb9bdi/pdb |
| Descriptor | GT10.2 glycan KO, Fab 45.2 Heavy Chain, Fab 45.2 Light Chain, ... (4 entities in total) |
| Functional Keywords | membrane-proximal external region (mper), hiv-1, germline targeting, b cell, germinal center, viral protein |
| Biological source | Mus musculus (house mouse) More |
| Total number of polymer chains | 6 |
| Total formula weight | 132022.41 |
| Authors | |
| Primary citation | Ray, R.,Schiffner, T.,Wang, X.,Yan, Y.,Rantalainen, K.,Lee, C.D.,Parikh, S.,Reyes, R.A.,Dale, G.A.,Lin, Y.C.,Pecetta, S.,Giguere, S.,Swanson, O.,Kratochvil, S.,Melzi, E.,Phung, I.,Madungwe, L.,Kalyuzhniy, O.,Warner, J.,Weldon, S.R.,Tingle, R.,Lamperti, E.,Kirsch, K.H.,Phelps, N.,Georgeson, E.,Adachi, Y.,Kubitz, M.,Nair, U.,Crotty, S.,Wilson, I.A.,Schief, W.R.,Batista, F.D. Affinity gaps among B cells in germinal centers drive the selection of MPER precursors. Nat.Immunol., 25:1083-1096, 2024 Cited by PubMed Abstract: Current prophylactic human immunodeficiency virus 1 (HIV-1) vaccine research aims to elicit broadly neutralizing antibodies (bnAbs). Membrane-proximal external region (MPER)-targeting bnAbs, such as 10E8, provide exceptionally broad neutralization, but some are autoreactive. Here, we generated humanized B cell antigen receptor knock-in mouse models to test whether a series of germline-targeting immunogens could drive MPER-specific precursors toward bnAbs. We found that recruitment of 10E8 precursors to germinal centers (GCs) required a minimum affinity for germline-targeting immunogens, but the GC residency of MPER precursors was brief due to displacement by higher-affinity endogenous B cell competitors. Higher-affinity germline-targeting immunogens extended the GC residency of MPER precursors, but robust long-term GC residency and maturation were only observed for MPER-HuGL18, an MPER precursor clonotype able to close the affinity gap with endogenous B cell competitors in the GC. Thus, germline-targeting immunogens could induce MPER-targeting antibodies, and B cell residency in the GC may be regulated by a precursor-competitor affinity gap. PubMed: 38816616DOI: 10.1038/s41590-024-01844-7 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.07 Å) |
Structure validation
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