en>ChrisGualtieri: /* External links */Remove stub template(s). Page is start class or higher. Also check for and do General Fixes + Checkwiki fixes using AWB

2013-12-18T14:43:17Z

External links: Remove stub template(s). Page is start class or higher. Also check for and do General Fixes + Checkwiki fixes using AWB

New page

In the context of biochemistry, '''avidity''' refers to the accumulated strength of ''multiple'' affinities of individual [[non-covalent]] binding interactions, such as between a protein receptor and its ligand, and is commonly referred to as functional affinity. As such, avidity is distinct from [[chemical affinity|affinity]], which describes the strength of a ''single'' interaction. However, because individual binding events increase the likelihood of other interactions to occur (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.
Biomolecules often form heterogenous complexes or homogenous [[oligomer]]s and multimers or [[polymer]]s.
If clustered proteins form an organized matrix, such as the [[clathrin]]-coat, the interaction is a described as [[matricity]].

==Antibody-antigen interaction==
Avidity is commonly applied to [[antibody]] interactions in which multiple antigen-binding sites simultaneously interact with the target [[antigen]]ic [[epitope]]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.<ref name="pmid19409036">{{cite journal| author=Rudnick SI, Adams GP| title=Affinity and avidity in antibody-based tumor targeting. | journal=Cancer Biother Radiopharm | year= 2009 | volume= 24 | issue= 2 | pages= 155–61 | pmid=19409036 | doi=10.1089/cbr.2009.0627 | pmc=2902227 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19409036 }}</ref> 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 between the reciprocal on-rate (kon, calculated from [[Association constant|Ka]]) and off-rate (koff, calculated from [[Dissociation constant|Kd]]) under specific concentrations of reactants in solution. There is always an inverse relationship between affinity and 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 (biochemistry)|receptor]]-[[Ligand (biochemistry)|ligand]] pairs, their interaction is also dependent on other structural and thermodynamic properties of reactants plus their orientation and immobilization.

There are multiple [[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]] of antigenic determinant and [[paratope]] of antigen-binding site of an antibody. Participating non-covalent interactions may include [[hydrogen bond]]s, [[ionic bond|electrostatic bond]]s, [[van der Waals force]]s and [[hydrophobic effect|hydrophobic force]]s.<ref>Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. Available from: http://www.ncbi.nlm.nih.gov/books/NBK10757/</ref>

Calculation of binding affinity for bimolecular reaction (1 antibody binding site per 1 antigen):

<math>[Ab] + [Ag] \leftrightharpoons [AbAg]</math>

where [Ab] is the [[antibody]] concentration and [Ag] is the [[antigen]] concentration, either in free ([Ab],[Ag]) or bound ([AbAg]) state.

calculation of association constant:
<math>K_a = \frac{k_{on}}{k_{off}} = \frac{[AbAg]}{[Ab][Ag]}</math>

calculation of dissociation constant:
<math>K_d = \frac{k_{off}}{k_{on}} = \frac{[Ab][Ag]}{[AbAg]}</math>

where ratio of ''k''a and ''k''d describes the binding affinity:

<math>K = \frac{K_a}{K_d} = \frac{[AbAg]}{[Ab][Ag]}</math>

where ''K'' is the [[equilibrium constant]].

==Application==
Avidity test for [[rubella virus]], [[Toxoplasma gondii]], [[cytomegalovirus]] (CMV), [[varicella-zoster virus]], human immunodeficiency virus ([[HIV]]), [[viral hepatitis|hepatitis viruses]], [[Epstein-Barr virus]], and others was developed few years ago. This test helps us to distinguish acute, recurrent or past infection by avidity of marker-specific [[IgG]]. Currently there are two avidity assay in use. These are well known chaotropic (conventional) assay and recently developed AVIcomp (avidity competition) assay.<ref name="pmid19129411">{{cite journal| author=Curdt I, Praast G, Sickinger E, Schultess J, Herold I, Braun HB et al.| title=Development of fully automated determination of marker-specific immunoglobulin G (IgG) avidity based on the avidity competition assay format: application for Abbott Architect cytomegalovirus and Toxo IgG Avidity assays. | journal=J Clin Microbiol | year= 2009 | volume= 47 | issue= 3 | pages= 603–13 | pmid=19129411 | doi=10.1128/JCM.01076-08 | pmc=2650902 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19129411 }}</ref>

==See also==
*[[Amino acid residue]]
*[[Epitope]]
*[[Fab region]]
*[[Hapten]]

==External links==
* {{MeshName|Antibody+Avidity}}

==References==
*Roitt, Ivan, ''et al.'', ''Immunology'', 6th edn, 2001, Mosby Publishers, page 72.
{{Reflist}}
Micro Class at SIUE

[[Category:Biophysics]]
[[Category:Proteins]]

Anomalous diffusion - Revision history

en>ChrisGualtieri: /* External links */Remove stub template(s). Page is start class or higher. Also check for and do General Fixes + Checkwiki fixes using AWB