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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 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, 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 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 thermodynamically
== History ==
A multimeric protiein's affinity for a ligand changes upon binding to a ligand, a process known as cooperativity. This phenomenon was first discovered by C. Bohr's analysis of hemoglobin, whose binding affinity for molecular oxygen increases as oxygen binds its subunits.<sup>[1]</sup> The [[Monod-Wyman-Changeux model|concerted model]] (or MWC model or symmetry model) provides a theoretical basis for understanding this phenomenon. The model proposes that multimeric proteins exist in two separate states, T and R. Upon ligand binding,
The KNF model (or induced fit model or sequential model) arose to address the possibility of differential binding states.<ref name=":1">{{Cite news|url=http://bio.libretexts.org/Core/Biochemistry/Binding/MODEL_BINDING_SYSTEMS#Free_Energy_and_Cooperativity|title=Model Binding Systems|date=2013-11-21|newspaper=Biology LibreTexts|access-date=2017-02-21|language=en-US}}</ref> Developed by Koshland, Némethy and Filmer in 1966, the KNF model describes cooperativity as a sequential process, where ligand binding alters the conformation, and thus the affinity, of proximal subunits of the protein, resulting in several different conformations that have varying affinities for a given ligand. This model suggests that the MWC model oversimplifies cooperativity in that it does not account for conformational changes of individual binding sites, opting instead to suggest a single, whole-protein conformational change.<ref name=":4" />
== Rules Guiding the KNF Model ==
The KNF model follows the structural theory of the induced fit model of
Two essential assumptions guide the KNF model:<ref name=":2">{{Cite book|url=https://www.worldcat.org/oclc/837581840|title=Structure and mechanism in protein science : a guide to enzyme catalysis and protein folding|last=Alan|first=Fersht,|publisher=Freeman|isbn=9780716732686|oclc=837581840}}</ref>
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