螺旋结构在髓鞘碱性蛋白免疫显性肽在多发性硬化症中高效IgM抗体识别中的作用

Role of Helical Structure in MBP Immunodominant Peptides for Efficient IgM Antibody Recognition in Multiple Sclerosis.

作者信息

Staśkiewicz Agnieszka, Quagliata Michael, Real-Fernandez Feliciana, Nuti Francesca, Lanzillo Roberta, Brescia-Morra Vincenzo, Rusche Hendrik, Jewginski Michal, Carotenuto Alfonso, Brancaccio Diego, Aharoni Rina, Arnon Ruth, Rovero Paolo, Latajka Rafal, Papini Anna Maria

机构信息

Interdepartmental Research Unit of Peptide and Protein Chemistry and Biology, Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy.

Department of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Science and Technology, Wroclaw, Poland.

出版信息

Front Chem. 2022 Jun 20;10:885180. doi: 10.3389/fchem.2022.885180. eCollection 2022.

DOI:10.3389/fchem.2022.885180

PMID:35795217

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9250970/

Abstract

The involvement of Myelin Basic Protein (MBP) in Multiple Sclerosis (MS) has been widely discussed in the literature. This intrinsically disordered protein has an interesting α-helix motif, which can be considered as a conformational epitope. In this work we investigate the importance of the helical structure in antibody recognition by MBP peptides of different lengths. Firstly, we synthesized the peptide MBP (81-106) (1) and observed that its elongation at both N- and C-termini, to obtain the peptide MBP (76-116) (2) improves IgM antibody recognition in SP-ELISA, but destabilizes the helical structure. Conversely, in competitive ELISA, MBP (81-106) (1) is recognized more efficiently by IgM antibodies than MBP (76-116) (2), possibly thanks to its more stable helical structure observed in CD and NMR conformational experiments. These results are discussed in terms of different performances of peptide antigens in the two ELISA formats tested.

摘要

髓鞘碱性蛋白（MBP）在多发性硬化症（MS）中的作用已在文献中得到广泛讨论。这种内在无序的蛋白质具有一个有趣的α-螺旋基序，可被视为一种构象表位。在这项工作中，我们研究了不同长度的MBP肽的螺旋结构在抗体识别中的重要性。首先，我们合成了肽MBP（81 - 106）（1），并观察到其在N端和C端的延伸，以获得肽MBP（76 - 116）（2），这在固相酶联免疫吸附测定（SP - ELISA）中提高了IgM抗体识别能力，但使螺旋结构不稳定。相反，在竞争性酶联免疫吸附测定中，IgM抗体对MBP（81 - 106）（1）的识别比MBP（76 - 116）（2）更有效，这可能得益于在圆二色性（CD）和核磁共振（NMR）构象实验中观察到的其更稳定的螺旋结构。根据所测试的两种酶联免疫吸附测定形式中肽抗原的不同表现对这些结果进行了讨论。