Department of Cancer Biology, Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Arturo Duperier 4, E-28029 Madrid, Spain.
Department of Biological Sciences, University of Calgary, 2500 University Dr. N.W., Calgary, Alberta T2N 1N4, Canada.
Biochim Biophys Acta Mol Cell Res. 2018 Mar;1865(3):507-521. doi: 10.1016/j.bbamcr.2017.12.004. Epub 2017 Dec 13.
Calmodulin (CaM) is a universal regulator for a huge number of proteins in all eukaryotic cells. Best known is its function as a calcium-dependent modulator of the activity of enzymes, such as protein kinases and phosphatases, as well as other signaling proteins including membrane receptors, channels and structural proteins. However, less well known is the fact that CaM can also function as a Ca-dependent adaptor protein, either by bridging between different domains of the same protein or by linking two identical or different target proteins together. These activities are possible due to the fact that CaM contains two independently-folded Ca binding lobes that are able to interact differentially and to some degree separately with targets proteins. In addition, CaM can interact with and regulates several proteins that function exclusively as adaptors. This review provides an overview over our present knowledge concerning the structural and functional aspects of the role of CaM as an adaptor protein and as a regulator of known adaptor/scaffold proteins.
钙调蛋白(CaM)是所有真核细胞中大量蛋白质的通用调节剂。其作为钙依赖性酶(如蛋白激酶和磷酸酶)活性调节剂的功能最为人熟知,此外,它还是其他信号蛋白(包括膜受体、通道和结构蛋白)的调节剂。然而,CaM 作为 Ca 依赖性衔接蛋白的功能却鲜为人知,它可以通过连接同一蛋白的不同结构域,或者将两个相同或不同的靶蛋白连接在一起,发挥衔接作用。CaM 之所以能够发挥这些功能,是因为它包含两个独立折叠的 Ca 结合结构域,这两个结构域能够以不同的方式与靶蛋白相互作用,并在一定程度上彼此独立。此外,CaM 还可以与仅作为衔接子的多种蛋白相互作用并对其进行调节。本文综述了 CaM 作为衔接蛋白以及调节已知衔接/支架蛋白的结构和功能方面的研究进展。