8fxj | pdb_00008fxj

Crystal structure of Fab460

spinqualitylabelsall models 8fxj, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8fxj is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: ACT, CL, GOL, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Broadly neutralizing antibodies (bnAbs) against HIV-1 target conserved envelope (Env) epitopes to block viral replication. Here, using structural analyses, we provide evidence to explain why a vaccine targeting the membrane-proximal external region (MPER) of HIV-1 elicits antibodies with human bnAb-like paratopes paradoxically unable to bind HIV-1. Unlike in natural infection, vaccination with MPER/liposomes lacks a necessary structure-based constraint to select for antibodies with an adequate approach angle. Consequently, the resulting Abs cannot physically access the MPER crawlspace on the virion surface. By studying naturally arising Abs, we further reveal that flexibility of the human IgG3 hinge mitigates the epitope inaccessibility and additionally facilitates Env spike protein crosslinking. Our results suggest that generation of IgG3 subtype class-switched B cells is a strategy for anti-MPER bnAb induction. Moreover, the findings illustrate the need to incorporate topological features of the target epitope in immunogen design. Inadequate structural constraint on Fab approach rather than paratope elicitation limits HIV-1 MPER vaccine utility.,Tan K, Chen J, Kaku Y, Wang Y, Donius L, Khan RA, Li X, Richter H, Seaman MS, Walz T, Hwang W, Reinherz EL, Kim M Nat Commun. 2023 Nov 8;14(1):7218. doi: 10.1038/s41467-023-42097-6. PMID:37940661 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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