11it | pdb_000011it
1332E5-RBD KP3.1.1 Complex Local Refine
Structural highlights
Publication Abstract from PubMedSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution reduces the efficacy of prophylactic vaccines and monoclonal antibody (mAb) therapies. To evaluate potency and breadth, receptor binding domain (RBD)-targeting neutralizing mAbs were identified from patient B cells using an Omicron KP3.1.1 Spike (S) protein bait. MAbs exhibiting the greatest neutralization potency (1332D4 and 1332E5) and binding breadth (1324A10 and 1316C10) were evaluated in greater detail. Cryo-electron microscopy (Cryo-EM) studies revealed 1332D4 and 1332E5 target RBD residue segments 439-446 and 498-506 of KP3.1.1 S, respectively. 1332E5 is a knob(498-506)-targeting class-1/4 mAb that exhibits pan-Omicron specificity but does not bind or neutralize ancestral Wuhan-1. Further analysis suggests mAbs generically defined as class 1/4 mAbs may be separated into two classes. Class 1/4 mAbs, like 1332E5, and class 4/1 mAbs that make extensive interactions with the class-4 epitope and limited contacts with the class-1 knob(498-596). Despite these differences, the specificity of both mAb classes can be altered by mutations in knob(498-506). Emergence of neutralizing RBD antibodies following Omicron infection with limited activity against ancestral SARS-CoV-2.,Piepenbrink MS, Ma Y, Panjwani S, Blake AR, Bell AM, Kizziah JL, Mahmoud SH, Ippolito GC, Erdmann NB, Goepfert PA, Martinez-Sobrido L, Kobie JJ, Walter MR iScience. 2026 Aug 11;29(8):117166. doi: 10.1016/j.isci.2026.117166. eCollection , 2026 Aug 21. PMID:42621159[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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