TY - JOUR

T1 - How human IgGs against myelin basic protein (MBP) recognize oligopeptides and MBP

AU - Belov, Sergey

AU - Buneva, Valentina N.

AU - Nevinsky, Georgy A.

N1 - Publisher Copyright: Copyright © 2017 John Wiley & Sons, Ltd.

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Myelin basic protein (MBP) is a major protein of myelin-proteolipid shell of axons, and it plays an important role in pathogenesis of multiple sclerosis. In the literature, there are no data on how antibodies recognize different protein antigens including MBP. A stepwise increase in ligand complexity was used to estimate the relative contributions of virtually every amino acid residue (AA) of a specific 12-mer LSRFSWGAEGQK oligopeptide corresponding to immunodominant sequence of MBP to the light chains and to intact anti-MBP IgGs from sera of patients with multiple sclerosis. It was shown that the minimal ligands of the light chains of IgGs are many different free AAs (Kd = 0.51–0.016 M), and each free AA interacts with the specific subsite of the light chain intended for recognition of this AA in specific LSRFSW oligopeptide. A gradual transition from Leu to LSRFSWGAEGQK leads to an increase in the affinity from 10−1 to 2.3 × 10−4 M because of additive interactions of the light chain with 6 AAs of this oligopeptide and then the affinity reaches plateau. The contributions of 6 various AAs to the affinity of the oligopeptide are different (Kd, M): 0.71 (S), 0.44 (R), 0.14 (F), 0.17 (S), and 0.62 (W). Affinity of nonspecific oligopeptides to the light chains of IgGs is significantly lower. Intact MBP interacts with both light and heavy chains of IgGs demonstrating 192-fold higher affinity than the specific oligopeptide. It is a first quantitative analysis of the mechanism of proteins recognition by antibodies. The thermodynamic model was constructed to describe the interactions of IgGs with MBP. The data obtained can be very useful for understanding how antibodies against many different proteins can recognize these proteins.

AB - Myelin basic protein (MBP) is a major protein of myelin-proteolipid shell of axons, and it plays an important role in pathogenesis of multiple sclerosis. In the literature, there are no data on how antibodies recognize different protein antigens including MBP. A stepwise increase in ligand complexity was used to estimate the relative contributions of virtually every amino acid residue (AA) of a specific 12-mer LSRFSWGAEGQK oligopeptide corresponding to immunodominant sequence of MBP to the light chains and to intact anti-MBP IgGs from sera of patients with multiple sclerosis. It was shown that the minimal ligands of the light chains of IgGs are many different free AAs (Kd = 0.51–0.016 M), and each free AA interacts with the specific subsite of the light chain intended for recognition of this AA in specific LSRFSW oligopeptide. A gradual transition from Leu to LSRFSWGAEGQK leads to an increase in the affinity from 10−1 to 2.3 × 10−4 M because of additive interactions of the light chain with 6 AAs of this oligopeptide and then the affinity reaches plateau. The contributions of 6 various AAs to the affinity of the oligopeptide are different (Kd, M): 0.71 (S), 0.44 (R), 0.14 (F), 0.17 (S), and 0.62 (W). Affinity of nonspecific oligopeptides to the light chains of IgGs is significantly lower. Intact MBP interacts with both light and heavy chains of IgGs demonstrating 192-fold higher affinity than the specific oligopeptide. It is a first quantitative analysis of the mechanism of proteins recognition by antibodies. The thermodynamic model was constructed to describe the interactions of IgGs with MBP. The data obtained can be very useful for understanding how antibodies against many different proteins can recognize these proteins.

KW - general regularities of protein recognition

KW - human anti-MBP antibodies

KW - myelin basic protein (MBP)

KW - recognition of peptides and MBP

KW - thermodynamic model of recognition

KW - SYSTEMIC-LUPUS-ERYTHEMATOSUS

KW - COMPLEX

KW - CRYSTAL-STRUCTURE

KW - MONOCLONAL-ANTIBODY

KW - VACCINIA VIRUS

KW - MULTIPLE-SCLEROSIS

KW - VIRUS TYPE-1 INTEGRASE

KW - STRUCTURAL BASIS

KW - DNA

KW - KINETIC BASIS

KW - Humans

KW - Middle Aged

KW - Oligopeptides/chemistry

KW - Chromatography, Thin Layer

KW - Thermodynamics

KW - Adult

KW - Cross-Linking Reagents/metabolism

KW - Immunoglobulin G/metabolism

KW - Amino Acid Sequence

KW - Immunoglobulin Light Chains/metabolism

KW - Electrophoresis, Polyacrylamide Gel

KW - Myelin Basic Protein/immunology

KW - Ligands

KW - Kinetics

UR - http://www.scopus.com/inward/record.url?scp=85018757735&partnerID=8YFLogxK

U2 - 10.1002/jmr.2637

DO - 10.1002/jmr.2637

M3 - Article

C2 - 28470769

AN - SCOPUS:85018757735

VL - 30

JO - Journal of Molecular Recognition

JF - Journal of Molecular Recognition

SN - 0952-3499

IS - 10

M1 - 2637

ER -