Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Arch Biochem Biophys. 2012 Mar 15;519(2):131-43. doi: 10.1016/j.abb.2011.11.020. Epub 2011 Dec 13.
Homo-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.
同聚寡聚蛋白组装体已知在天然条件下参与动态的缔合/解离平衡，从而形成组装状态的平衡。这种四级结构平衡可以通过共价修饰或配体的非共价结合以生理上显著的方式受到影响。本综述通过 20 世纪和 21 世纪的思想演变，探讨了同聚寡聚平衡与配体非共价结合的变构调节之间的关系。描述了一种动态的四级结构平衡，其中解离状态可以具有不能重新组装到原始多聚体的替代构象；替代构象决定了功能上不同的有限化学计量的交替多聚体的组装。不同组装体之间的功能区别提供了变构作用的机制。解离的要求将这种变构调节的形态素模型与经典的 MWC 协同和 KNF 顺序模型区分开来。这些模型与早期的解离变构模型一起进行了描述。鉴定作为多种天然四级结构组装体平衡存在的蛋白质有可能确定变构调节的新靶标，这对进一步理解和/或控制蛋白质结构和功能具有重要意义。因此，提出了识别可能使用变构形态素模型的蛋白质的基本原理，并列出了一些发表的数据表明该机制可能起作用的蛋白质。
