ライソ酵素との複合体におけるサメ単一ドメイン抗体V領域の結晶構造

Robyn L Stanfield¹, Helen Dooley, Martin F Flajnik

¹Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Science (New York, N.Y.)

|August 21, 2004

まとめ

軟骨魚は,適応免疫のためのユニークな新しい抗原受容体 (IgNARs) を持っている. 単一ドメインのIgNAR変数領域は,従来の抗体と同様に,高い親和性を持つ抗原を結合します.

科学分野:

免疫学免疫学とは
構造生物学構造生物学とは
進化生物学の進化生物学について

背景:

軟骨魚は,適応免疫を持つ古代の脊椎動物を表しています.
新しい抗原受容体 (IgNARs) は,これらの魚に特有の重鎖ホモジメロ免疫グロブリンです.
IgNAR変数 (V) ドメインは,単一の免疫グロブリンドメインを使用して抗原を認識します.

研究の目的:

IgNAR Vドメインによる抗原認識の構造的基礎を解明する.
IgNAR Vドメイン構造と従来の抗体との結合インターフェースを比較する.

主な方法:

1.45アングストームの解像度のX線結晶学.
I型IgNAR Vドメインと鶏卵白のリゾーシム (HEL) の間の複合形成.

主要な成果:

HELに結合したIgnar Vドメインの結晶構造を決定した.
IgNAR Vドメインは最小の抗原結合単位であり,従来の補完性を決定する領域が1つ欠けています.
その単純さにもかかわらず,Ignar VドメインはHEL.ELに対するナノモラー親和性を表しています.
結合インターフェースのサイズは,従来の抗体と比較できます.

結論:

IgNAR Vドメインは,軟骨魚における簡素化されながらも有効な抗原結合モジュールである.
この構造は,抗体ドメインの進化と抗原認識の洞察を提供します.

さらに関連する動画

09:39

Targeted Antibody Blocking by a Dual-Functional Conjugate of Antigenic Peptide and Fc-III Mimetics (DCAF)

Published on: September 17, 2019

10:17

Creating Highly Specific Chemically Induced Protein Dimerization Systems by Stepwise Phage Selection of a Combinatorial Single-Domain Antibody Library

Published on: January 14, 2020

関連する概念動画

01:10

Antibody Structure

Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...

02:26

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...

01:10

Antibody Structure

01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:

関連する実験動画