Structural and functional anatomy of the globular domain of complement protein C1q

Uday Kishore1, Rohit Ghai, Trevor J Greenhough

  • 1Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK. ukishore@hotmail.com

Immunology Letters
|September 25, 2004
PubMed

Insights

Complement C1q, a key immune system protein, recognizes diverse ligands through its globular domain (gC1q). Recent research reveals this domain

Area of Science:

  • Immunology
  • Structural Biology
  • Biochemistry

Background:

  • C1q initiates the classical complement pathway, bridging innate and adaptive immunity.
  • C1q functions as a pattern recognition molecule, binding various ligands via its globular head (gC1q).
  • The gC1q domain comprises heterotrimeric A, B, and C chains (ghA, ghB, ghC).

Purpose of the Study:

  • To investigate the modular organization and ligand specificity of the C1q gC1q domain.
  • To elucidate the structure-function relationships within the gC1q domain.
  • To explore how molecular structure influences C1q's versatile ligand recognition.

Main Methods:

  • Recombinant expression of ghA, ghB, and ghC chains.
  • X-ray crystallography of the gC1q domain.
  • Molecular modeling and protein engineering studies.

Main Results:

  • The gC1q domain exhibits a modular organization.
  • Individual ghA, ghB, and ghC chains display differential ligand specificities.
  • Structural and modeling studies reveal how modularity, charge, and spatial arrangement enable versatile ligand binding.

Conclusions:

  • The gC1q domain's structure supports its broad ligand recognition capabilities.
  • Understanding C1q's structure-function relationship provides insights into complement activation.
  • Further research is needed to address emerging questions regarding gC1q function.

Related Concept Videos

Complement System01:27

Complement System

The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a membrane...
Globular Proteins01:27

Globular Proteins

In organisms, proteins are the most abundant macromolecules. They act as the building blocks of life and play various crucial roles in the body. Proteins can be broadly classified into two distinct subtypes based on their shape and solubilities: globular proteins and fibrous proteins.
Globular proteins serve many important physiological functions, such as acting as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be soluble in the aqueous...
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.
Conservation of Protein Domains Over Different Proteins02:26

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...