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Crystal Structure of an influenza A hemagglutinin antibody Fab variant CH67:1203d4 chimeraCrystal Structure of an influenza A hemagglutinin antibody Fab variant CH67:1203d4 chimera
Structural highlights
Publication Abstract from PubMedThe amount of antibody (Ab) variable gene sequence information is expanding rapidly, but our ability to predict the function of Abs from sequence alone is limited. Here, we describe a sequence-to-function prediction method that couples structural data for a single Ab/antigen (Ag) complex with repertoire data. We used a position-specific structure-scoring matrix (P3SM) incorporating structure-prediction scores from Rosetta to identify Ab variable loops that have predicted structural similarity to the influenza virus-specific human Ab CH65. The P3SM approach identified new members of this Ab class. Recombinant Ab expression, crystallography, and virus inhibition assays showed that the HCDR3 loops of the newly identified Abs possessed similar structure and antiviral activity as the comparator CH65. This approach enables discovery of new human Abs with desired structure and function using cDNA repertoires that are obtained readily with current amplicon sequencing techniques. Identification of Structurally Related Antibodies in Antibody Sequence Databases Using Rosetta-Derived Position-Specific Scoring.,Finn JA, Dong J, Sevy AM, Parrish E, Gilchuk I, Nargi R, Scarlett-Jones M, Reichard W, Bombardi R, Voss TG, Meiler J, Crowe JE Jr Structure. 2020 Oct 6;28(10):1124-1130.e5. doi: 10.1016/j.str.2020.07.012. Epub, 2020 Aug 11. PMID:32783953[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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