In
biochemistry
Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, a ...
, avidity refers to the accumulated strength of ''multiple'' affinities of individual
non-covalent binding interactions, such as between a protein receptor and its
ligand
In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...
, and is commonly referred to as functional affinity. Avidity differs from
affinity
Affinity may refer to:
Commerce, finance and law
* Affinity (law), kinship by marriage
* Affinity analysis, a market research and business management technique
* Affinity Credit Union, a Saskatchewan-based credit union
* Affinity Equity Pa ...
, which describes the strength of a ''single'' interaction. However, because individual binding events increase the likelihood of occurrence of other interactions (i.e., increase the local concentration of each binding partner in proximity to the binding site), avidity should not be thought of as the mere sum of its constituent affinities but as the combined effect of all affinities participating in the biomolecular interaction. A particular important aspect relates to the phenomenon of 'avidity entropy'. Biomolecules often form heterogenous complexes or homogeneous
oligomer
In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relativ ...
s and multimers or
polymer
A polymer () is a chemical substance, substance or material that consists of very large molecules, or macromolecules, that are constituted by many repeat unit, repeating subunits derived from one or more species of monomers. Due to their br ...
s. If clustered proteins form an organized matrix, such as the
clathrin-coat, the interaction is described as a
matricity.
Antibody-antigen interaction
Avidity is commonly applied to
antibody
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...
interactions in which multiple antigen-binding sites simultaneously interact with the target
antigen
In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.
...
ic
epitope
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although e ...
s, often in multimerized structures. Individually, each binding interaction may be readily broken; however, when many binding interactions are present at the same time, transient unbinding of a single site does not allow the molecule to diffuse away, and binding of that weak interaction is likely to be restored.
Each antibody has at least two antigen-binding sites, therefore antibodies are bivalent to multivalent. Avidity (functional affinity) is the accumulated strength of multiple affinities.
For example,
IgM is said to have low affinity but high avidity because it has 10 weak binding sites for antigen as opposed to the 2 stronger binding sites of
IgG,
IgE and
IgD with higher single binding affinities.
Affinity
Binding affinity is a measure of dynamic equilibrium of the ratio of on-rate (k
on) and off-rate (k
off) under specific concentrations of reactants. The affinity constant,
Ka, is the inverse of the dissociation constant,
Kd. The strength of complex formation in solution is related to the
stability constants of complexes
In coordination chemistry, a stability constant (also called formation constant or binding constant) is an equilibrium constant for the formation of a complex in solution. It is a measure of the strength of the interaction between the reagents tha ...
, however in case of large biomolecules, such as
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...
-
ligand
In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...
pairs, their interaction is also dependent on other structural and thermodynamic properties of reactants plus their orientation and immobilization.
There are several
methods to investigate protein–protein interactions existing with differences in immobilization of each reactant in 2D or 3D orientation. The measured affinities are stored in public databases, such as the
Ki Database and
BindingDB. As an example, affinity is the binding strength between the complex structures of the
epitope
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although e ...
of antigenic determinant and
paratope of antigen-binding site of an antibody. Participating non-covalent interactions may include
hydrogen bond
In chemistry, a hydrogen bond (H-bond) is a specific type of molecular interaction that exhibits partial covalent character and cannot be described as a purely electrostatic force. It occurs when a hydrogen (H) atom, Covalent bond, covalently b ...
s,
electrostatic bonds,
van der Waals force
In molecular physics and chemistry, the van der Waals force (sometimes van der Waals' force) is a distance-dependent interaction between atoms or molecules. Unlike ionic or covalent bonds, these attractions do not result from a chemical elec ...
s and
hydrophobic effect
The hydrophobic effect is the observed tendency of nonpolar substances to aggregate in an aqueous solution and to be excluded by water. The word hydrophobic literally means "water-fearing", and it describes the segregation of water and nonpola ...
s.
Calculation of binding affinity for bimolecular reaction (1 antibody binding site per 1 antigen):
:
b+ g<=> bAg
A bag, also known regionally as a sack, is a common tool in the form of a floppy container, typically made of cloth, leather, bamboo, paper, or plastic. The use of bags predates recorded history, with the earliest bags being lengths of animal s ...
/chem>
where bis the antibody
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...
concentration and gis the antigen
In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.
...
concentration, either in free ( b g or bound (bAg
A bag, also known regionally as a sack, is a common tool in the form of a floppy container, typically made of cloth, leather, bamboo, paper, or plastic. The use of bags predates recorded history, with the earliest bags being lengths of animal s ...
state.
calculation of association constant (or equilibrium constant
The equilibrium constant of a chemical reaction is the value of its reaction quotient at chemical equilibrium, a state approached by a dynamic chemical system after sufficient time has elapsed at which its composition has no measurable tendency ...
):
:
calculation of dissociation constant:
:
Application
Avidity tests for rubella virus, ''Toxoplasma gondii
''Toxoplasma gondii'' () is a species of parasitic alveolate that causes toxoplasmosis. Found worldwide, ''T. gondii'' is capable of infecting virtually all warm-blooded animals, but members of the cat family (felidae) are the only known d ...
'', cytomegalovirus
''Cytomegalovirus'' (CMV) (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order '' Herpesvirales'', in the family '' Herpesviridae'', in the subfamily '' Betaherp ...
(CMV), varicella zoster virus
Varicella zoster virus (VZV), also known as human herpesvirus 3 (HHV-3, HHV3), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting children and young adults, and shingles (herpes zos ...
, human immunodeficiency virus ( HIV), hepatitis viruses, Epstein–Barr virus
The Epstein–Barr virus (EBV), also known as human herpesvirus 4 (HHV-4), is one of the nine known Herpesviridae#Human herpesvirus types, human herpesvirus types in the Herpesviridae, herpes family, and is one of the most common viruses in ...
, and others were developed a few years ago. These tests help to distinguish acute, recurrent or past infection by avidity of marker-specific IgG. Currently there are two avidity assays in use. These are the well known chaotropic (conventional) assay and the recently developed AVIcomp (avidity competition) assay.
See also
* Amino acid residue
*Epitope
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although e ...
* Fab region
* Hapten
A number of technologies exist to characterise the avidity of molecular interactions including switchSENSE and surface plasmon resonance.
References
Further reading
*
External links
* {{MeshName, Antibody+Avidity
Biophysics
Protein structure