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Related Concept Videos

Antibody Structure01:10

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...
Antibody Structure01:10

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...
Antibody Structure and Classes01:25

Antibody Structure and Classes

Antibodies, also known as immunoglobulins, are produced by B cells in response to foreign substances, such as bacteria and viruses. These proteins are critical for recognizing and neutralizing these substances, protecting the body from potential harm.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
Immunoglobulin-like Cell Adhesion Molecules01:31

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Bones of the Upper Limb: Humerus01:19

Bones of the Upper Limb: Humerus

The upper limb consists of the arm, forearm, wrist, and hand bones. The humerus is the single bone of the upper arm region. Proximally, it has a large, spherical, smooth head that articulates with the glenoid cavity of the scapula to form the glenohumeral or shoulder joint. The margin of the head is the anatomical neck, a residual epiphyseal plate. Laterally it extends to form bony projections called the greater tubercle and the lesser tubercle. Next to the tubercles is the surgical neck, a...
Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...

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A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
04:47

A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies

Published on: February 23, 2018

Engineering upper hinge improves stability and effector function of a human IgG1.

Boxu Yan1, Daniel Boyd, Timothy Kaschak

  • 1Department of Pharma Technical Development, Genentech, Oceanside, California 92056, USA. byan1027@gmail.com

The Journal of Biological Chemistry
|December 29, 2011
PubMed
Summary
This summary is machine-generated.

Radical attacks degrade IgG1 antibodies. Substituting histidine with tyrosine at position 229 significantly enhances antibody stability and function, improving FcγRIII binding and ADCC activity.

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Optimized Negative Staining: a High-throughput Protocol for Examining Small and Asymmetric Protein Structure by Electron Microscopy
09:37

Optimized Negative Staining: a High-throughput Protocol for Examining Small and Asymmetric Protein Structure by Electron Microscopy

Published on: August 15, 2014

Area of Science:

  • Biochemistry
  • Immunology
  • Protein Engineering

Background:

  • The upper hinge region of IgG1 antibodies is susceptible to radical-induced degradation, affecting heavy-light chain linkage and hinge cleavage.
  • Understanding the mechanisms of this degradation is crucial for improving antibody stability and therapeutic efficacy.

Purpose of the Study:

  • To investigate the roles of Asp and His residues in the upper hinge of IgG1 in radical-induced degradation.
  • To explore strategies for enhancing IgG1 antibody stability and function through targeted mutations.

Main Methods:

  • Design and analysis of nine IgG1 mutants to probe the function of upper hinge Asp and His residues.
  • Assessment of heavy-light chain linkage integrity and hinge cleavage under radical attack conditions.
  • Evaluation of antibody binding to FcγRIII receptors and antibody-dependent cell-mediated cytotoxicity (ADCC) activity.

Main Results:

  • Heavy-light chain linkage breakage appears independent of His(229) and may involve direct electron transfer from Cys(231).
  • Substitution of His(229) with Tyr inhibited hinge cleavage by 98%, significantly enhancing antibody stability.
  • The Tyr substitution increased FcγRIII binding 2-3 fold and improved ADCC activity 2-fold, with comparable pharmacokinetics to wild-type IgG1.

Conclusions:

  • The His(229) to Tyr substitution offers a promising strategy for engineering more stable and functional IgG1 antibodies.
  • The lower redox potential of Tyr likely contributes to its ability to inhibit radical-induced hinge degradation.
  • These findings have significant implications for antibody engineering and the development of next-generation antibody therapeutics.