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

被引：0

作者：

Staskiewicz, Agnieszka ^{[1
,2
]}

Quagliata, Michael ^{[1
]}

Real-Fernandez, Feliciana ^{[1
]}

Nuti, Francesca ^{[1
]}

Lanzillo, Roberta ^{[3
]}

Brescia-Morra, Vincenzo ^{[3
]}

Rusche, Hendrik ^{[4
,5
,9
]}

Jewginski, Michal ^{[2
]}

Carotenuto, Alfonso ^{[6
]}

Brancaccio, Diego ^{[6
]}

Aharoni, Rina ^{[7
]}

Arnon, Ruth ^{[7
]}

Rovero, Paolo ^{[8
]}

Latajka, Rafal ^{[2
]}

Papini, Anna Maria ^{[1
,5
,9
]}

机构：

[1] Univ Florence, Dept Chem Ugo Schiff, Interdept Res Unit Peptide & Prot Chem & Biol, Sesto Fiorentino, Italy

[2] Wroclaw Univ Sci & Technol, Fac Chem, Dept Bioorgan Chem, Wroclaw, Poland

[3] Univ Naples Federico II, Multiple Sclerosis Clin Care & Res Ctr, Dept Neurosci Reprod Sci & Odontostomatol, Naples, Italy

[4] Fischer Analyt GmbH, Weiler, Germany

[5] CY Cergy Paris Univ, CY PeptLab Platform Peptide & Prot Chem & Biol, CNRS, Neuville Oise, France

[6] Univ Naples Federico II, Dept Pharm, Naples, Italy

[7] Weizmann Inst Sci, Dept Immunol, Rehovot, Israel

[8] Univ Florence, Dept NeuroFarBa, Interdept Res Unit Peptide & Prot Chem & Biol, Sesto Fiorentino, Italy

[9] CY Cergy Paris Univ, CNRS, UMR 8076 CNRS BioCIS, Neuville Oise, France

来源：

FRONTIERS IN CHEMISTRY | 2022年 / 10卷

关键词：

multiple sclerosis; circular dichroism; immune response; synthetic helical peptides; myelin basic protein antigen; peptide-antigen based ELISA; NMR; MYELIN BASIC-PROTEIN; CEREBROSPINAL-FLUID; CIRCULAR-DICHROISM; SYNTHETIC PEPTIDE; CROSS-REACTIVITY; FINE SPECIFICITY; EPITOPE; AUTOANTIBODIES; BIOMARKERS; STABILIZATION;

D O I：

10.3389/fchem.2022.885180

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 alpha-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.

引用

页数：11

共 60 条

[1] Solution Nuclear Magnetic Resonance Structure and Molecular Dynamics Simulations of a Murine 18.5 kDa Myelin Basic Protein Segment (S72-S107) in Association with Dodecylphosphocholine Micelles
Ahmed, Mumdooh A. M.
De Avila, Miguel
Polverini, Eugenia
Bessonov, Kyrylo
Bamm, Vladimir V.
Harauz, George
[J]. BIOCHEMISTRY, 2012, 51 (38) : 7475 - 7487
[2] An immunodominant epitope of myelin basic protein is an amphipathic α-helix
Bates, IR
Feix, JB
Boggs, JM
Harauz, G
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (07) : 5757 - 5764
[3] Beniac D R, 1999, Mol Cell Biol Res Commun, V1, P48, DOI 10.1006/mcbr.1999.0111
[4] Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event
Berger, T
Rubner, P
Schautzer, F
Egg, R
Ulmer, H
Mayringer, I
Dilitz, E
Deisenhammer, F
Reindl, M
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2003, 349 (02) : 139 - 145
[5] Myelin basic protein: a multifunctional protein
Boggs, J. M.
[J]. CELLULAR AND MOLECULAR LIFE SCIENCES, 2006, 63 (17) : 1945 - 1961
[6] Boggs JM, 1999, J NEUROSCI RES, V57, P529, DOI 10.1002/(SICI)1097-4547(19990815)57:4<529::AID-JNR12>3.3.CO
[7] 2-S
[8] STUDIES OF SYNTHETIC HELICAL PEPTIDES USING CIRCULAR-DICHROISM AND NUCLEAR-MAGNETIC-RESONANCE
BRADLEY, EK
THOMASON, JF
COHEN, FE
KOSEN, PA
KUNTZ, ID
[J]. JOURNAL OF MOLECULAR BIOLOGY, 1990, 215 (04) : 607 - 622
[9] COHERENCE TRANSFER BY ISOTROPIC MIXING - APPLICATION TO PROTON CORRELATION SPECTROSCOPY
BRAUNSCHWEILER, L
ERNST, RR
[J]. JOURNAL OF MAGNETIC RESONANCE, 1983, 53 (03) : 521 - 528
[10] Conformational studies of a synthetic peptide from the putative lipid-binding domain of bovine milk component PP3
Campagna, S
Vitoux, B
Humbert, G
Girardet, JM
Linden, G
Haertle, T
Gaillard, JL
[J]. JOURNAL OF DAIRY SCIENCE, 1998, 81 (12) : 3139 - 3148

← 1 2 3 4 5 6 →