IQ-motif selectivity in human IQGAP2 and IQGAP3: binding of calmodulin and myosin essential light chain
IQ-motif selectivity in human IQGAP2 and IQGAP3: binding of calmodulin and myosin essential light chain
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DOI：
10.1042/bsr20100123
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发表时间：
2011-10-01
影响因子：
4
通讯作者：
Timson, David J.
中科院分区：
文献类型：
--
作者：
Atcheson, Erwan;Hamilton, Elaine;Timson, David J.
IQGAP [含IQ基序的GAP（GTP酶激活蛋白）]家族成员是在细胞信号传导和细胞骨架之间的界面起作用的真核蛋白。因此，它们从各种信号通路收集大量输入。一个关键的结合伴侣是钙敏感蛋白CaM（钙调蛋白）。该蛋白主要通过一系列位于IQGAP的一级序列中间的IQ基序结合。在一些IQGAP中，这些基序也为钙调蛋白样蛋白如肌球蛋白必需轻链和S100 B提供结合位点。使用合成肽和天然凝胶电泳，从人IQGAP 2和IQGAP 3的IQ基序的结合特性已被映射。IQGAP 2中的第二和第三个IQ基序以及IQGAP 3中的所有四个IQ基序在钙离子存在下与CaM相互作用。然而，在相互作用的类型上存在差异：虽然一些IQ基序能够与在实验条件下稳定的CaM形成复合物，但其他基序形成了更短暂的相互作用。IQGAP 2和IQGAP 3的第一个IQ基序在不存在钙的情况下与CaM形成瞬时相互作用，IQGAP 3的第一个基序与肌球蛋白必需轻链MIc 1 sa形成瞬时相互作用。这些IQ基序均不与S100 B相互作用。分子模拟表明，除了来自IQGAP 2的第一个以外，所有的IQ基序在溶液中形成α-螺旋。这些结果扩展了我们对IQ基序对CaM和相关蛋白质的选择性的认识。
The IQGAP [IQ-motif-containing GAP (GTPase-activating protein)] family members are eukaryotic proteins that act at the interface between cellular signalling and the cytoskeleton. As such they collect numerous inputs from a variety of signalling pathways. A key binding partner is the calcium-sensing protein CaM (calmodulin). This protein binds mainly through a series of IQ-motifs which are located towards the middle of the primary sequence of the IQGAPs. In some IQGAPs, these motifs also provide binding sites for CaM-like proteins such as myosin essential light chain and S100B. Using synthetic peptides and native gel electrophoresis, the binding properties of the IQ-motifs from human IQGAP2 and IQGAP3 have been mapped. The second and third IQ-motifs in IQGAP2 and all four of the IQ-motifs of IQGAP3 interacted with CaM in the presence of calcium ions. However, there were differences in the type of interaction: while some IQ-motifs were able to form complexes with CaM which were stable under the conditions of the experiment, others formed more transient interactions. The first IQ-motifs from IQGAP2 and IQGAP3 formed transient interactions with CaM in the absence of calcium and the first motif from IQGAP3 formed a transient interaction with the myosin essential light chain MIc1sa. None of these IQ-motifs interacted with S100B. Molecular modelling suggested that all of the IQ-motifs, except the first one from IQGAP2 formed alpha-helices in solution. These results extend our knowledge of the selectivity of IQ-motifs for CaM and related proteins.