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Selwood T , Jaffe EK
Dynamic dissociating homo-oligomers and the control of protein function
Arch Biochem Biophys. 2012 Mar 15;519(2) :131-43
PMID: 22182754 PMCID: PMC3298769
AbstractHomo-oligomeric protein assemblies are known to participate in dynamic association/disassociation equilibria under native conditions, thus creating an equilibrium of assembly states. Such quaternary structure equilibria may be influenced in a physiologically significant manner either by covalent modification or by the non-covalent binding of ligands. This review follows the evolution of ideas about homo-oligomeric equilibria through the 20th and into the 21st centuries and the relationship of these equilibria to allosteric regulation by the non-covalent binding of ligands. A dynamic quaternary structure equilibria is described where the dissociated state can have alternate conformations that cannot reassociate to the original multimer; the alternate conformations dictate assembly to functionally distinct alternate multimers of finite stoichiometry. The functional distinction between different assemblies provides a mechanism for allostery. The requirement for dissociation distinguishes this morpheein model of allosteric regulation from the classical MWC concerted and KNF sequential models. These models are described alongside earlier dissociating allosteric models. The identification of proteins that exist as an equilibrium of diverse native quaternary structure assemblies has the potential to define new targets for allosteric modulation with significant consequences for further understanding and/or controlling protein structure and function. Thus, a rationale for identifying proteins that may use the morpheein model of allostery is presented and a selection of proteins for which published data suggests this mechanism may be operative are listed.
NotesSelwood, Trevor Jaffe, Eileen K P30CA006927/CA/NCI NIH HHS/United States R01E5003654/PHS HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review United States Archives of biochemistry and biophysics Arch Biochem Biophys. 2012 Mar 15;519(2):131-43. Epub 2011 Dec 13.