Sequential model: Difference between revisions

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The '''sequential model''' (also known as the '''[[Induced fit#Induced fit model|KNF model]] ''') is a theory that describes co-operativity[[cooperativity]] of [[protein subunit]]s<ref name=":3">Koshland, D.E., Némethy, G. and Filmer, D. (1966) Comparison of experimental binding data and theoretical models in proteins containing subunits.

Biochemistry 5, 365–385. [http://pubs.acs.org/doi/abs/10.1021/bi00865a047 DOI: 10.1021/bi00865a047]</ref> It postulates that a protein's conformation changes with each binding of a [[Ligand (biochemistry)|ligand]], thus sequentially changing its affinity for the ligand at neighboring binding sites.

[[File:KNF_model.gif|thumb|Visual representation of the KNF model in a tetrameric protein.|433x433px]]

==Overview==

This model for [[allosteric regulation]] of [[Enzyme|enzymes]] suggests that the [[Protein subunit|subunits]] of multimeric proteins have two conformational states.<ref name=":3" /> The binding of the ligand causes conformational change in the other subunits of the multimeric protein. Although the subunits go through conformational changes independently (as opposed to in the [[MWC model]]), the switch of one subunit makes the other subunits more likely to change, by reducing the energy needed for subsequent subunits to undergo the same conformational change. In elaboration, the binding of a ligand to one subunit changes the protein's shape, thereby making it more [[Thermodynamic free energy|thermodynamically favorable]] for the other subunits to switch conformation to the high affinity state. Ligand binding may also result in negative cooperativity, or a reduced affinity for the ligand at the next binding site, a feature that makes the KNF model distinct from the MWC model, which onlysuggests offersonly positive cooperativity.<ref name=":0">{{Cite journal|last=Koshland|first=Daniel E.|last2=Hamadani|first2=Kambiz|date=2002-12-06|title=Proteomics and Models for Enzyme Cooperativity|url=http://www.jbc.org/content/277/49/46841|journal=Journal of Biological Chemistry|language=en|volume=277|issue=49|pages=46841–46844|doi=10.1074/jbc.R200014200|issn=0021-9258|pmid=12189158}}</ref><ref name=":5">{{Cite journal|last=Henis|first=Y I|last2=Levitzki|first2=A|date=1980-09-01|title=Mechanism of negative cooperativity in glyceraldehyde-3-phosphate dehydrogenase deduced from ligand competition experiments.|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC349994/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=77|issue=9|pages=5055–5059|issn=0027-8424|pmc=PMC349994|pmid=6933545}}</ref> It is named KNF after Koshland, Némethy and Filmer, who first suggested the model .<ref name=":3" />

== History ==

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Unlike the MWC model, the KNF model offers the possibility of "negative cooperativity".<ref name=":0" /><ref name=":2" /> This term describes a reduction in the affinity of the other binding sites of a protein for a ligand after the binding of one or more of the ligand to its subunits. The MWC model only allows for positive cooperativity, where a single conformational switch from the T to R states results in an increase in affinity for the ligand at unligated binding sites. Ligand binding to the T state thus cannot increase the amount of the protein in the T, or low-affinity, state.

Negative cooperativity is observed in a number of biologically significant molecules, including tyrosyl-tRNA synthetase and glyceraldehyde-3-phosphate dehydrogenase.<ref name=":5" /><ref name=":2" /> In fact, in a systematic literature review performed in 2002 by Koshland and Hamadi, the same literature review that coined i³ cooperativity, negatively cooperating proteins are seen to compose slightly less than 50% of scientifically studied proteins that exhibit cooperativity, while positively cooperating proteins compose the other, slightly greater than 50%.<ref name=":0" />

==References==