Phosphatidylinositol-4,5 bisphosphate (PIP(2)) inhibits apo-calmodulin binding to protein 4.1.
Phosphatidylinositol-4,5 bisphosphate (PIP(2)) inhibits apo-calmodulin binding to protein 4.1.
复制标题
磷脂酰肌醇-4,5 二磷酸 (PIP(2)) 抑制脱辅基钙调蛋白与蛋白 4.1 的结合。
DOI：
10.1016/j.bbrc.2014.02.121
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发表时间：
2014
影响因子：
3.1
通讯作者：
Takakuwa,Yuichi
中科院分区：
文献类型：
--
作者：
Nunomura,Wataru;Gascard,Philippe;Wakui,Hideki;Takakuwa,Yuichi
膜骨架蛋白4.1R80在红细胞可塑性调节中起关键作用。蛋白4.1R80与跨膜蛋白如血型糖蛋白C（GPC）的相互作用受Ca 2+饱和的钙调蛋白（Ca 2 +/CaM）的调节，通过同时与位于4.1R80（H·R30）N端30 kDa FERM结构域的短肽（pep 11; A264 KKLWKVCVEHHTFFRL）和丝氨酸残基（Ser 185）结合。我们先前已经证明，CaM与H·R30的结合是Ca 2+非依赖性的，并且CaM与H·R30的结合负责维持H·R30的β-折叠结构。然而，负责调节CaM与H·R30结合的机制仍然未知。为了研究这一点，我们利用了果蝇科卡勒结构的相似性和差异性。人4.1R80的同源物，即pep 11序列保守，但Ser 185残基被丙氨酸残基取代。我们发现Coracle的H·R30同源结构域Cor 30也以Ca 2+非依赖的方式与CaM结合，并且Ca 2 +/CaM复合物不影响Cor 30与跨膜蛋白GPC的结合。我们还证明了H·R30和Cor 30都与磷脂酰肌醇-4，5二磷酸（PIP 2）和其他磷脂物质结合，并且PIP 2抑制游离Ca 2+的CaM，但不抑制Ca 2+饱和的CaM与Cor 30的结合。我们认为PIP 2可能在进化过程中作为apo-CaM与4.1R80结合的调节剂发挥重要作用。
Membrane skeletal protein 4.1R80plays a key role in regulation of erythrocyte plasticity. Protein 4.1R80interactions with transmembrane proteins, such as glycophorin C (GPC), are regulated by Ca2+-saturated calmodulin (Ca2+/CaM) through simultaneous binding to a short peptide (pep11; A264KKLWKVCVEHHTFFRL) and a serine residue (Ser185), both located in the N-terminal 30 kDa FERM domain of 4.1R80(H·R30). We have previously demonstrated that CaM binding to H·R30 is Ca2+-independent and that CaM binding to H·R30 is responsible for the maintenance of H·R30 β-sheet structure. However, the mechanisms responsible for the regulation of CaM binding to H·R30 are still unknown. To investigate this, we took advantage of similarities and differences in the structure of Coracle, theDrosophilasp. homologue of human 4.1R80, i.e. conservation of the pep11 sequence but substitution of the Ser185residue with an alanine residue. We show that the H·R30 homologue domain of Coracle, Cor30, also binds to CaM in a Ca2+-independent manner and that the Ca2+/CaM complex does not affect Cor30 binding to the transmembrane protein GPC. We also document that both H·R30 and Cor30 bind to phosphatidylinositol-4,5 bisphosphate (PIP2) and other phospholipid species and that that PIP2inhibits Ca2+-free CaM but not Ca2+-saturated CaM binding to Cor30. We conclude that PIP2may play an important role as a modulator of apo-CaM binding to 4.1R80throughout evolution.