PEP-19, an Intrinsically Disordered Regulator of Calmodulin Signaling
PEP-19, an Intrinsically Disordered Regulator of Calmodulin Signaling
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DOI：
10.1074/jbc.m808067200
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发表时间：
2009-03-20
影响因子：
4.8
通讯作者：
Putkey, John A.
中科院分区：
文献类型：
--
作者：
Kleerekoper, Quinn K.;Putkey, John A.
PEP-19是一种小的钙调蛋白（CaM）结合蛋白，它极大地增加了Ca2+与CaM c结构域的结合和解离率，这一效应是由PEP-19中的酸性/IQ序列介导的。我们在这里用核磁共振表明PEP-19是一个本质上无序的蛋白质，但其残余结构定位于其酸性/IQ基序。我们还发现，PEP-19与载脂蛋白-CaM结合的k（on）和k（off）速率至少比与Ca2+-CaM结合慢50倍。这些数据表明，内在紊乱赋予PEP-19可塑性，使其能够通过不同的结构模式与apo-或Ca2+- cam结合，并且酸性/IQ序列中残余结构的构象选择可能促进复合物的形成。
PEP-19 is a small calmodulin (CaM)-binding protein that greatly increases the rates of association and dissociation of Ca2+ from the C-domain of CaM, an effect that is mediated by an acidic/IQ sequence in PEP-19. We show here using NMR that PEP-19 is an intrinsically disordered protein, but with residual structure localized to its acidic/IQ motif. We also show that the k(on) and k(off) rates for binding PEP-19 to apo-CaM are at least 50-fold slower than for binding to Ca2+-CaM. These data indicate that intrinsic disorder confers plasticity that allows PEP-19 to bind to either apo- or Ca2+-CaM via different structural modes, and that complex formation may be facilitated by conformational selection of residual structure in the acidic/IQ sequence.