Structural highlights
Publication Abstract from PubMedThe membrane-proximal external region (MPER) of gp41 harbors the epitope recognized by the broadly neutralizing anti-HIV 2F5 antibody, a research focus in HIV-1 vaccine development. In this work we analyze the structure and immunogenic properties of MPERp, a peptide vaccine including: i) the complete sequence protected from proteolysis by the 2F5 paratope; ii) downstream residues postulated to establish weak contacts with the CDR-H3 loop of the antibody, which are believed to be crucial for neutralization; and iii) an aromatic-rich anchor to the membrane-interface. MPERp structures solved in dodecylphosphocholine micelles and 25 % 1,1,1,3,3,3-hexafluoro-2-propanol (v/v) confirmed folding of the complete 2F5 epitope within continuous kinked helices. Infrared spectroscopy (IR) measurements demonstrated the retention of main helical conformations in immunogenic formulations based on alum, Freund's adjuvant or two different types of liposomes. Binding to membrane-inserted MPERp, IR, Molecular Dynamics Simulations and characterization of the immune responses further suggested that packed helical bundles partially inserted into the lipid bilayer, rather than monomeric helices adsorbed to the membrane-interface, could encompass effective MPER peptide vaccines. Together, our data constitute a proof-of-concept to support MPER-based peptides in combination with liposomes as stand-alone immunogens, and suggest new approaches for structure-aided MPER vaccine development. Structure and Immunogenicity of a Peptide Vaccine Including the Complete HIV-1 gp41 2F5 Epitope. Implications for Antibody Recognition Mechanism and Immunogen Design.,Serrano S, Araujo A, Apellaniz B, Bryson S, Carravilla P, De la Arada I, Huarte N, Rujas E, Pai EF, Arrondo JL, Domene C, Jimenez MA, Nieva JL J Biol Chem. 2014 Jan 15. PMID:24429284[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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This page was last modified 06:55, 14 May 2014.