Enhanced antigenicity of a four-contact-residue epitope of the measles virus hemagglutinin protein by phage display libraries: evidence of a helical structure in the putative active site

被引:22
作者
Deroo, S
El Kasmi, KC
Fournier, P
Theisen, D
Brons, RHC
Herrmann, M
Desmet, J
Muller, CP
机构
[1] Lab Natl Sante, L-1011 Luxembourg, Luxembourg
[2] Univ Tubingen, Med Fak, D-72076 Tubingen, Germany
[3] Nat Wissensch & Med Inst, D-72770 Reutlingen, Germany
[4] Katholieke Univ Leuven, Interdisciplinary Res Ctr, B-8500 Kortrijk, Belgium
关键词
peptide; linear epitope; helix structure; neutralising antibodies; measles virus; hemagglutinin protein;
D O I
10.1016/S0161-5890(98)00057-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Antigenicity and conformational propensities of synthetic peptides corresponding to the sequential epitope H236-255 of the measles virus hemagglutinin protein were investigated. This epitope corresponds to the neutralising and protective monoclonal antibody BH129 and includes Arg243, implicated in CD46-down-regulation and Arg253 that has been mapped to the putative enzymatic site. Fine mapping with truncation-, elongation-, Gly- and Ala-substitution analogues defined EL-QL as the critical residues of the minimal epitope S(244)ELSQL(249). CD spectra of peptides, comparison with the 3D-structure of homologous sequences, and prediction algorithms suggested a helical structure with the contact residues E245L-QL(249) located on the protein surface. Mimotopes obtained with a 6-mer phage display library contained a consensus Pro (important for binding) instead of Ser,,, of the wild-type sequence (irrelevant for binding). The kink induced by Pro seemed to be essential to bring the 4 contact-residues in the mimotopes and in the corresponding short peptides together. CD analysis and prediction algorithms suggested that non-helical conformations of the phage insert and of the peptides may favourably mimic the antigenic helical turns of the wild-type sequence, resulting in an up to 135 times higher antigenicity of the mAb towards the mimotope peptides. (C) 1998 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:435 / 443
页数:9
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