Kiran Uday, Regur Phanindranath, Kreutz Michael R, Sharma Yogendra, Chakraborty Asima
CSIR-Centre for Cellular and Molecular Biology (CCMB) , Uppal Road, Hyderabad 500007, India.
RG Neuroplasticity, Leibniz Institute for Neurobiology , Brenneckestrasse 6, 39118 Magdeburg, Germany.
Biochemistry. 2017 May 16;56(19):2467-2476. doi: 10.1021/acs.biochem.7b00132. Epub 2017 May 5.
A crucial event in calcium signaling is the transition of a calcium sensor from the apo (Ca free) to the holo (Ca-saturated) state. Caldendrin (CDD) is a neuronal Ca-binding protein with two functional (EF3 and EF4) and two atypical (EF1 and EF2), non-Ca-binding EF-hand motifs. During the transition from the apo to the holo state, guided by the stepwise filling of Ca, the protein passes through distinct states and acquires a stable conformational state when only EF3 is occupied by Ca. This state is characterized by a Ca-derived structural gain in EF3 with destabilization of the EF4 motif. At higher Ca levels, when Ca fills in EF4, the motif regains stability. EF3 controls initial Ca binding and dictates structural destabilization of EF4. It is likely that this unexpected intermotif communication will have an impact on Ca-dependent target interactions.
钙信号传导中的一个关键事件是钙传感器从无钙（脱辅基）状态转变为钙饱和（全酶）状态。钙调蛋白（CDD）是一种神经元钙结合蛋白，具有两个功能性（EF3和EF4）和两个非典型（EF1和EF2）、不结合钙的EF手基序。在从脱辅基状态转变为全酶状态的过程中，在钙逐步填充的引导下，蛋白质会经历不同的状态，并且当只有EF3被钙占据时会获得稳定的构象状态。这种状态的特征是EF3中由钙产生的结构增益以及EF4基序的不稳定。在更高的钙水平下，当钙填充到EF4中时，该基序恢复稳定性。EF3控制初始钙结合并决定EF4的结构不稳定。这种意外的基序间通讯可能会对钙依赖性靶标相互作用产生影响。
