Cardiovascular Research Institute, University of California, San Francisco, CA 94158-2330, USA.
Structure. 2010 Dec 8;18(12):1617-31. doi: 10.1016/j.str.2010.09.012.
Calcium-binding protein 1 (CaBP1), a calmodulin (CaM) homolog, endows certain voltage-gated calcium channels (Ca(V)s) with unusual properties. CaBP1 inhibits Ca(V)1.2 calcium-dependent inactivation (CDI) and introduces calcium-dependent facilitation (CDF). Here, we show that the ability of CaBP1 to inhibit Ca(V)1.2 CDI and induce CDF arises from interaction between the CaBP1 N-lobe and interlobe linker residue Glu94. Unlike CaM, where functional EF hands are essential for channel modulation, CDI inhibition does not require functional CaBP1 EF hands. Furthermore, CaBP1-mediated CDF has different molecular requirements than CaM-mediated CDF. Overall, the data show that CaBP1 comprises two structural modules having separate functions: similar to CaM, the CaBP1 C-lobe serves as a high-affinity anchor that binds the Ca(V)1.2 IQ domain at a site that overlaps with the Ca²+/CaM C-lobe site, whereas the N-lobe/linker module houses the elements required for channel modulation. Discovery of this division provides the framework for understanding how CaBP1 regulates Ca(V)s.
钙结合蛋白 1（CaBP1）是钙调蛋白（CaM）的同源物，使某些电压门控钙通道（Ca(V)s）具有独特的性质。CaBP1 抑制 Ca(V)1.2 钙依赖性失活（CDI）并引入钙依赖性易化（CDF）。在这里，我们表明，CaBP1 抑制 Ca(V)1.2 CDI 和诱导 CDF 的能力源自 CaBP1 N 结构域和结构域间连接残基 Glu94 之间的相互作用。与 CaM 不同，功能 EF 手对于通道调节至关重要，CDI 抑制不需要功能性 CaBP1 EF 手。此外，CaBP1 介导的 CDF 具有与 CaM 介导的 CDF 不同的分子要求。总的来说，数据表明 CaBP1 包含两个具有独立功能的结构模块：类似于 CaM，CaBP1 的 C 结构域充当高亲和力的锚，将 Ca(V)1.2 IQ 结构域结合在与 Ca²⁺/CaM C 结构域结合位点重叠的位点，而 N 结构域/连接模块包含调节通道所需的元件。这种划分的发现为理解 CaBP1 如何调节 Ca(V)s 提供了框架。
