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Neutralizing and protective monoclonal antibodies (mAbs) were used to fine-map the highlyconserved hemagglutinin noose epitope (H379–410, HNE) of themeasles virus. Short peptides mimicking this epitope were previouslyshown to induce virus-neutralizing antibodies [El Kasmi et al. (2000) J. Gen. Virol.81, 729–735]. The epitope contains three cys-teine residues, two of which (Cys386 and Cys394) form a disulfide bridge critical for antibodybinding. | Eur. J. Biochem. 270 1515-1527 2003 FEBS 2003 doi 10.1046 j.1432-1033.2003.03517.x Functional fine-mapping and molecular modeling of a conserved loop epitope of the measles virus hemagglutinin protein Mike M. Putz1 2 Johan Hoebeke3 Wim Ammerlaan1 Serge Schneider4 and Claude P. Muller1 5 1 Department of Immunology Laboratoire National de Sante Luxembourg 2Fakultat fur Chemie und Pharmazie Universitat Tubingen Germany UPR 9021 CNRS Immunologie et Chimie Therapeutiques Institut de Biologie Moleculaire et Cellulaire Strasbourg France 4Division de Toxicologie Laboratoire National de Sante Centre Universitaire de Luxembourg Luxembourg 5Medizinische Fakultat Universitat Tubingen Germany Neutralizing and protective monoclonal antibodies mAbs were used to fine-map the highly consrveed hemagglutinin noose epitope H379-410 HNE of the measles virus. Short peptides mimicking this epitope were previously shown to induce virus-neutralizing antibodies El Kasmi et al. 2000 J. Gen. Virol. 81 729-735 . The epitope contains three cysteine residues two of which Cys386 and Cys394 form a disulfide bridge critical for antibodybinding. Substitution and truncation analogues revealed four residues critical for binding Lys387 Gly388 Gln391 and Glu395 and suggested the binding motif X7C KR GX AINQ QX2CEX5 for three distinct protective mAbs. This motif was found in more than 90 of the wild-type viruses. An independent molecular model of the core epitope predicted an amphiphilic loop displaying a remarkably stable and rigid loop conformation. The three hydrophilic contact residues Lys387 Gln391 and Glu395 pointed on the virus towards the solvent-exposed side of the planar loop and the permissive hydrophobic residues Ile390 Ala392 and Leu393 towards the solvent-hidden side of the loop precluding antibody binding. The high allinity Kd 7.60 nM of the mAb BH216 for the peptide suggests a high structural resemblance of the peptide with the natural epitope and indicates that most interactions with the
