3q1s
HIV-1 neutralizing antibody Z13e1 in complex with epitope display proteinHIV-1 neutralizing antibody Z13e1 in complex with epitope display protein
Structural highlights
FunctionIL22_HUMAN Cytokine that contributes to the inflammatory response in vivo. Publication Abstract from PubMedAntibody Z13e1 is a relatively broadly neutralizing anti-human immunodeficiency virus type 1 antibody that recognizes the membrane-proximal external region (MPER) of the human immunodeficiency virus type 1 envelope glycoprotein gp41. Based on the crystal structure of an MPER epitope peptide in complex with Z13e1 Fab, we identified an unrelated protein, interleukin (IL)-22, with a surface-exposed region that is structurally homologous in its backbone to the gp41 Z13e1 epitope. By grafting the gp41 Z13e1 epitope sequence onto the structurally homologous region in IL-22, we engineered a novel protein (Z13-IL22-2) that contains the MPER epitope sequence for use as a potential immunogen and as a reagent for the detection of Z13e1-like antibodies. The Z13-IL22-2 protein binds Fab Z13e1 with a K(d) of 73 nM. The crystal structure of Z13-IL22-2 in complex with Fab Z13e1 shows that the epitope region is faithfully replicated in the Fab-bound scaffold protein; however, isothermal calorimetry studies indicate that Fab binding to Z13-IL22-2 is not a lock-and-key event, leaving open the question of whether conformational changes upon binding occur in the Fab, in Z13-IL-22, or in both. Structure-Based Design of a Protein Immunogen that Displays an HIV-1 gp41 Neutralizing Epitope.,Stanfield RL, Julien JP, Pejchal R, Gach JS, Zwick MB, Wilson IA J Mol Biol. 2011 Dec 2;414(3):460-76. Epub 2011 Oct 15. PMID:22033480[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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