Exploration of antibody allosteric networks of glycans and proteins

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15981
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
• Research Institution: Institute for Molecular Science
• Principal Investigator: Yanaka Saeko 分子科学研究所, 生命・錯体分子科学研究領域, 助教 (80722777)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 免疫グロブリンG / Fc領域 / 糖鎖 / MDシミュレーション / 核磁気共鳴法 / アロステリックネットワーク

Outline of Final Research Achievements

Antibodies are glycoproteins that trigger effector functions upon antigen recognition and are responsible for the elimination of foreign substances in the immune system. Glycans attached to antibodies are closely linked to their effector functions, and there can be more than 100 different glycoforms. The glycans of antibodies form intramolecular networks that are integrated with the protein portion, and it is supposed that subtle changes in the glycan structure can affect the intramolecular network, causing structural changes at unexpected distal sites and modulating the effector functions. This study explored the "allosteric network" of glycans and proteins in the antibody molecule through the integration of experimental and theoretical approaches, highlighting the relationship between the dynamics and functions of the network.

Free Research Field

タンパク質工学

Academic Significance and Societal Importance of the Research Achievements

糖鎖を含めた抗体の構造解析はいくつかの取り組みが報告されているが、それらは断片的な現象論的記述にとどまっており、分子の動的3次元構造の観点に立って、糖鎖構造のバリエーションと機能を結びつける系統的な研究は国内外を通じて行われていない。
本研究により、これまで各論的な経験に基づいて行われているバイオ医薬の糖鎖バリエーションの品質管理に科学的根拠がもたらされるとともに、次世代抗体医薬の創成に向けての体系的な設計指針を与えることが可能となるものと期待される。