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 ...
, 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 ( 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 ele ...
, and is commonly referred to as functional affinity. Avidity differs from
affinity, 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 relat ...
s and multimers or
polymer
A polymer (; Greek ''poly-'', "many" + '' -mer'', "part")
is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic and ...
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), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and Viral disease, viruses. The antibody recognizes a unique m ...
interactions in which multiple antigen-binding sites simultaneously interact with the target
antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain 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 epitope is the specific piece of the antigen to which an antibody binds. The ...
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
Immunoglobulin D (IgD) is an antibody isotype that makes up about 1% of proteins in the plasma membranes of immature B-lymphocytes where it is usually co-expressed with another cell surface antibody called IgM. IgD is also produced in a secreted f ...
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, however in case of large biomolecules, such as
receptor-
ligand
In coordination chemistry, a ligand is an ion or molecule ( 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 ele ...
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
The Ki Database (or Ki DB) is a public domain database of published binding affinities (''K''i) of drugs and chemical compounds for receptors, neurotransmitter transporters, ion channels, and enzymes
Enzymes () are proteins that act as ...
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 epitope is the specific piece of the antigen to which an antibody binds. The ...
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 (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing ...
s,
electrostatic bond
Ionic bonding is a type of chemical bonding that involves the electrostatic attraction between oppositely charged ions, or between two atoms with sharply different electronegativities, and is the primary interaction occurring in ionic compound ...
s,
van der Waals force
In molecular physics, the 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 electronic bond; they are comparatively weak and t ...
s and
hydrophobic forces.
Calculation of binding affinity for bimolecular reaction (1 antibody binding site per 1 antigen):
:
b+ g<=> bAg/chem>
where bis the antibody
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and Viral disease, viruses. The antibody recognizes a unique m ...
concentration and gis the antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain 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 state.
calculation of association constant (or equilibrium constant):
:
calculation of dissociation constant:
:
Application
Avidity tests for rubella virus, ''Toxoplasma gondii
''Toxoplasma gondii'' () is an obligate intracellular parasitic protozoan (specifically an apicomplexan) that causes toxoplasmosis. Found worldwide, ''T. gondii'' is capable of infecting virtually all warm-blooded animals, but felids, such ...
'', 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 '' Betahe ...
(CMV), varicella zoster virus
Varicella-zoster virus (VZV), also known as human herpesvirus 3 (HHV-3, HHV3) or ''Human alphaherpesvirus 3'' (taxonomically), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting chil ...
, human immunodeficiency virus (HIV
The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immu ...
), hepatitis viruses, Epstein–Barr virus
The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus.
It is ...
, 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 epitope is the specific piece of the antigen to which an antibody binds. The ...
* 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