University Basel, Basel, Switzerland.
Adv Exp Med Biol. 2013;961:27-33. doi: 10.1007/978-1-4614-4756-6_3.
Ion transport performed by the Na(+)/Ca(2+) exchanger (NCX) is regulated via its cytosolic Ca(2+)-binding domains, CBD1 and CBD2, which act as sensors for intracellular Ca(2+). Striking differences in the electrostatic potential of the Ca(2+)-bound and Ca(2+)-free forms turn the CBD1 and CBD2 Ca(2+)-binding sites into electrostatic switches similar to those of C(2) domains. Binding of Ca(2+) with high affinity to CBD1 induces a conformational change that is relayed to the transmembrane domain and thereby initiates Na(+)/Ca(2+) exchange. The Ca(2+) concentration at which this conformational change occurs is determined by the Ca(2+) affinities of the strictly conserved CBD1 Ca(2+)-binding sites that are modulated by an adjacent, variable region of CBD2. In contrast, the Ca(2+)-binding properties of CBD2 depend on the isoform and the type of residues in the Ca(2+)-binding sites, encoded by a mutually exclusive exon. This second electrostatic switch, formed by CBD2, appears to be required for sustained Na(+)/Ca(2+) exchange and may allow tailored, tissue-specific exchange activities.
由 Na(+)/Ca(2+) 交换器 (NCX) 执行的离子转运受其胞质 Ca(2+) 结合域 CBD1 和 CBD2 调节，这些域作为细胞内 Ca(2+) 的传感器。结合 Ca(2+) 后，结合域 CBD1 和 CBD2 的静电势发生显著变化，使它们成为类似于 C(2)结构域的静电开关。与 CBD1 高亲和力结合 Ca(2+) 会诱导构象变化，这种变化会被传递到跨膜域，从而启动 Na(+)/Ca(2+) 交换。这种构象变化发生的 Ca(2+) 浓度取决于 CBD1 Ca(2+) 结合位点的 Ca(2+) 亲和力，而 CBD1 Ca(2+) 结合位点的 Ca(2+) 亲和力受 CBD2 中相邻可变区域的调节。相比之下，CBD2 的 Ca(2+) 结合特性取决于其同工型和 Ca(2+) 结合位点中的残基类型，这些特性由相互排斥的外显子编码。由 CBD2 形成的第二个静电开关似乎是持续进行 Na(+)/Ca(2+) 交换所必需的，并且可能允许进行针对特定组织的交换活动。
