抗体结合位点在重链和轻链可变区的定位。
Localization of antibody-combining sites within the variable portions of heavy and light chains.
作者信息
Inbar D, Hochman J, Givol D
出版信息
Proc Natl Acad Sci U S A. 1972 Sep;69(9):2659-62. doi: 10.1073/pnas.69.9.2659.
Abstract
The Fab'-fragment of a mouse IgA-myeloma (protein-315) was split by pepsin to yield a smaller fragment that retained the anti-2,4-dinitrophenyl activity of the intact protein. This fragment, which we call Fv, has a molecular weight of about 30,000 (half that of Fab'), and is composed of two polypeptide chains (molecular weight 14,000) held together by noncovalent bonds. The N-terminal sequence of Fv suggests that it is composed of the N-terminal half of Fab', and consists of the variable portions of the heavy and light chains. Since Fv has about one binding site with the same association constant as Fab', this experiment provides direct evidence that the antibody site in this protein is contained entirely in the variable portion, and is independent of the constant portion, of the molecule.
摘要
小鼠IgA骨髓瘤（蛋白-315）的Fab'片段被胃蛋白酶裂解，产生一个较小的片段，该片段保留了完整蛋白的抗2,4-二硝基苯基活性。我们将这个片段称为Fv，其分子量约为30,000（Fab'的一半），由两条通过非共价键结合在一起的多肽链（分子量14,000）组成。Fv的N端序列表明它由Fab'的N端一半组成，由重链和轻链的可变部分组成。由于Fv具有约一个与Fab'相同缔合常数的结合位点，该实验提供了直接证据，证明该蛋白中的抗体位点完全包含在分子的可变部分中，并且与恒定部分无关。
相似文献
1
Localization of antibody-combining sites within the variable portions of heavy and light chains.抗体结合位点在重链和轻链可变区的定位。
Proc Natl Acad Sci U S A. 1972 Sep;69(9):2659-62. doi: 10.1073/pnas.69.9.2659.
2
An active antibody fragment (Fv) composed of the variable portions of heavy and light chains.一种由重链和轻链可变部分组成的活性抗体片段（Fv）。
Biochemistry. 1973 Mar 13;12(6):1130-5. doi: 10.1021/bi00730a018.
3
Crystallization with hapten of the Fab' fragment from a mouse IgA myeloma protein with antidinitrophenyl activity.具有抗二硝基苯基活性的小鼠IgA骨髓瘤蛋白Fab'片段与半抗原的结晶。
J Biol Chem. 1971 Oct 25;246(20):6272-5.
4
Preparation of Fv fragment from the mouse myeloma XRPC-25 immunoglobulin possessing anti-dinitrophenyl activity.从具有抗二硝基苯基活性的小鼠骨髓瘤XRPC - 25免疫球蛋白制备Fv片段。
Biochemistry. 1976 Apr 6;15(7):1591-4. doi: 10.1021/bi00652a033.
5
Localization of idiotypic antigenic determinants in the Fv region of murine myeloma protein MOPC-315.小鼠骨髓瘤蛋白MOPC - 315的Fv区域中独特型抗原决定簇的定位
Proc Natl Acad Sci U S A. 1973 May;70(5):1585-7. doi: 10.1073/pnas.70.5.1585.
6
Conformational change(s) induced in sheep calcium-dependent antibody upon interaction with homologous polypeptide antigen. I. Hydrogen-exchange studies of immunoglobulin G and (Fab') 2 fragment.绵羊钙依赖性抗体与同源多肽抗原相互作用时诱导的构象变化。I. 免疫球蛋白G和（Fab'）2片段的氢交换研究。
Biochemistry. 1972 Aug 29;11(18):3312-20. doi: 10.1021/bi00768a002.
7
Human myeloma IgG half-molecules. Structural and antigenic analyses,人骨髓瘤IgG半分子。结构与抗原分析
Biochemistry. 1975 May 20;14(10):2157-63. doi: 10.1021/bi00681a018.
8
Peptides from the dinitrophenyl binding site of myeloma IgA of mouse MOPC 315.
Immunol Commun. 1974;3(3):265-74. doi: 10.3109/08820137409057323.
9
The three-dimensional structure of the fab' fragment of a human myeloma immunoglobulin at 2.0-angstrom resolution.人骨髓瘤免疫球蛋白Fab'片段在2.0埃分辨率下的三维结构。
Proc Natl Acad Sci U S A. 1974 Sep;71(9):3440-4. doi: 10.1073/pnas.71.9.3440.
10
Amino-acid sequence of the variable region of the heavy (alpha) chain of a mouse myeloma protein with anti-hapten activity.具有抗半抗原活性的小鼠骨髓瘤蛋白重链（α链）可变区的氨基酸序列。
Proc Natl Acad Sci U S A. 1974 Apr;71(4):1123-7. doi: 10.1073/pnas.71.4.1123.
引用本文的文献
1
AI-driven antibody design with generative diffusion models: current insights and future directions.基于生成扩散模型的人工智能驱动抗体设计：当前见解与未来方向。
Acta Pharmacol Sin. 2025 Mar;46(3):565-574. doi: 10.1038/s41401-024-01380-y. Epub 2024 Sep 30.
2
Therapeutic Role of Neutralizing Antibody for the Treatment against SARS-CoV-2 and Its Emerging Variants: A Clinical and Pre-Clinical Perspective.中和抗体在治疗新冠病毒及其新变种中的作用：临床与临床前视角
Vaccines (Basel). 2022 Sep 26;10(10):1612. doi: 10.3390/vaccines10101612.
3
Bispecific T Cell Engagers for the Treatment of Multiple Myeloma: Achievements and Challenges.用于治疗多发性骨髓瘤的双特异性T细胞衔接器：成就与挑战
Cancers (Basel). 2021 Jun 8;13(12):2853. doi: 10.3390/cancers13122853.
4
Vaccines: Underlying Principles of Design and Testing.疫苗：设计和测试的基本原则。
Clin Pharmacol Ther. 2021 Apr;109(4):987-999. doi: 10.1002/cpt.2207. Epub 2021 Mar 11.
5
Integrative proteomics identifies thousands of distinct, multi-epitope, and high-affinity nanobodies.综合蛋白质组学鉴定出数千种独特的、多表位和高亲和力的纳米抗体。
Cell Syst. 2021 Mar 17;12(3):220-234.e9. doi: 10.1016/j.cels.2021.01.003. Epub 2021 Feb 15.
6
A genetically encoded probe for imaging nascent and mature HA-tagged proteins in vivo.一种用于体内成像新生和成熟 HA 标记蛋白的基因编码探针。
Nat Commun. 2019 Jul 3;10(1):2947. doi: 10.1038/s41467-019-10846-1.
7
Structural modules of the stress-induced protein HflX: an outlook on its evolution and biological role.应激诱导蛋白HflX的结构模块：对其进化和生物学作用的展望
Curr Genet. 2019 Apr;65(2):363-370. doi: 10.1007/s00294-018-0905-x. Epub 2018 Nov 17.
8
Rethinking the INN system for therapeutic antibodies.重新思考治疗性抗体的国际非专利药品名称（INN）系统。
MAbs. 2017 Jan;9(1):5-11. doi: 10.1080/19420862.2016.1255520. Epub 2016 Nov 3.
9
Development trends for therapeutic antibody fragments.治疗性抗体片段的发展趋势。
Nat Biotechnol. 2009 Apr;27(4):331-7. doi: 10.1038/nbt0409-331.
10
Expression, purification and characterization of B72.3 Fv fragments.B72.3 Fv片段的表达、纯化及特性分析
Biochem J. 1993 Mar 15;290 ( Pt 3)(Pt 3):723-9. doi: 10.1042/bj2900723.
本文引用的文献
1
Isolation of a low molecular weight antibody fraction containing the antideterminant.
Folia Biol (Praha). 1962 Jun;8:147-51.
2
The hydrolysis of rabbit y-globulin and antibodies with crystalline papain.用结晶木瓜蛋白酶对兔γ球蛋白和抗体进行水解。
Biochem J. 1959 Sep;73(1):119-26. doi: 10.1042/bj0730119.
3
RECOVERY OF SPECIFIC ACTIVITY AFTER COMPLETE UNFOLDING AND REDUCTION OF AN ANTIBODY FRAGMENT.抗体片段完全展开和还原后比活性的恢复
Proc Natl Acad Sci U S A. 1965 Mar;53(3):524-32. doi: 10.1073/pnas.53.3.524.
4
DETERMINATION OF ANTIBODY AFFINITY FOR HAPTENS AND ANTIGENS BY MEANS OF FLUORESCENCE QUENCHING.通过荧光猝灭法测定抗体对半抗原和抗原的亲和力
Methods Med Res. 1964;10:115-21.
5
RECOVERY OF ANTIGENIC SPECIFICITY AFTER DENATURATION AND COMPLETE REDUCTION OF DISULFIDES IN A PAPAIN FRAGMENT OF ANTIBODY.抗体木瓜蛋白酶片段中变性及二硫键完全还原后抗原特异性的恢复
Proc Natl Acad Sci U S A. 1964 Oct;52(4):1099-106. doi: 10.1073/pnas.52.4.1099.
6
THE ARRANGEMENT OF THE PEPTIDE CHAINS IN GAMMA-GLOBULIN.γ球蛋白中肽链的排列
Biochem J. 1963 Aug;88(2):220-8. doi: 10.1042/bj0880220.
7
Spectroscopic determination of tryptophan and tyrosine in proteins.蛋白质中色氨酸和酪氨酸的光谱测定
Biochemistry. 1967 Jul;6(7):1948-54. doi: 10.1021/bi00859a010.
8
Acrylamide-gel electrophorograms by mechanical fractionation: radioactive adenovirus proteins.通过机械分级分离得到的丙烯酰胺凝胶电泳图谱：放射性腺病毒蛋白
Science. 1966 Feb 25;151(3713):988-90. doi: 10.1126/science.151.3713.988.
9
Attempts to locate complementarity-determining residues in the variable positions of light and heavy chains.尝试在轻链和重链可变区定位互补决定残基。
Ann N Y Acad Sci. 1971 Dec 31;190:382-93. doi: 10.1111/j.1749-6632.1971.tb13550.x.
10
Amino acid sequence of the light chain from a mouse myeloma protein with anti-hapten activity: evidence for a third type of light chain.具有抗半抗原活性的小鼠骨髓瘤蛋白轻链的氨基酸序列：第三种轻链类型的证据
Proc Natl Acad Sci U S A. 1971 Nov;68(11):2623-6. doi: 10.1073/pnas.68.11.2623.
Zotero 插件