Department of Biochemistry and Molecular Biology, McGovern Medical at UTHealth, 6431 Fannin, Houston, Texas 77030, USA.
Nat Commun. 2016 Nov 23;7:13583. doi: 10.1038/ncomms13583.
PEP-19 is a small protein that increases the rates of Ca binding to the C-domain of calmodulin (CaM) by an unknown mechanism. Although an IQ motif promotes binding to CaM, an acidic sequence in PEP-19 is required to modulate Ca binding and to sensitize HeLa cells to ATP-induced Ca release. Here, we report the NMR solution structure of a complex between PEP-19 and the C-domain of apo CaM. The acidic sequence of PEP-19 associates between helices E and F of CaM via hydrophobic interactions. This allows the acidic side chains in PEP-19 to extend toward the solvent and form a negatively charged surface that resembles a catcher's mitt near Ca binding loop III of CaM. The topology and gradients of negative electrostatic surface potential support a mechanism by which PEP-19 increases the rate of Ca binding to the C-domain of CaM by 'catching' and electrostatically steering Ca to site III.
PEP-19 是一种小蛋白，通过未知机制提高钙与钙调蛋白 (CaM) C 结构域结合的速率。尽管 IQ 基序促进与 CaM 的结合，但 PEP-19 中的酸性序列对于调节钙结合和使 HeLa 细胞对 ATP 诱导的钙释放敏感是必需的。在这里，我们报告了 PEP-19 与 apo CaM C 结构域之间复合物的 NMR 溶液结构。PEP-19 的酸性序列通过疏水相互作用与 CaM 的 E 和 F 螺旋之间发生关联。这使得 PEP-19 中的酸性侧链能够伸向溶剂并形成一个带负电荷的表面，该表面类似于 CaM 钙结合环 III 附近的捕手手套。负静电表面电势的拓扑结构和梯度支持了一种机制，即 PEP-19 通过“捕获”和静电引导 Ca 到 III 位点来增加 Ca 与 CaM 的 C 结构域结合的速率。
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