...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Sarcolipin regulates sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) by binding to transmembrane helices alone or in association with phospholamban.
【24h】

Sarcolipin regulates sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) by binding to transmembrane helices alone or in association with phospholamban.

机译：Sarcolipin通过单独或与phosphorlamban结合跨膜螺旋来调节sarco（endo）质网Ca2 + -ATPase（SERCA）。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Phospholamban (PLN), a regulator of sarco(endo)plasmic reticulum Ca(2+)-ATPases (SERCAs), interacts with both the cytosolic N domain and transmembrane helices M2, M4, M6, and M9 of SERCA. Amino acids in the transmembrane domain of PLN that are predicted to interact with SERCA1a are conserved in sarcolipin (SLN), a functional PLN homologue. Accordingly, the effects of critical mutations in SERCA1a, PLN, and NF-SLN (SLN tagged N-terminally with a FLAG epitope) on NF-SLN/SERCA1a and PLN/NF-SLN/SERCA1a interactions were compared. Critical mutations in SERCA1a and NF-SLN diminished functional interactions between SERCA1a and NF-SLN, indicating that NF-SLN and PLN interact with some of the same amino acids in SERCA1a. Mutations in PLN or NF-SLN affected the amount of SERCA1a that was coimmunoprecipitated in each complex with antibodies against either PLN or SLN, but not the pattern of coimmunoprecipitation. PLN mutations had more dramatic effects on SERCA1a coimmunoprecipitation than SLN mutations, suggesting that PLN dominates in the primary interaction with SERCA1a. Coimmunoprecipitation also confirmed that PLN and NF-SLN form a heterodimer that interacts with SERCA1a in a regulatory fashion to form a very stable PLN/NF-SLN/SERCA1a complex. Modeling showed that the SLN/SERCA1a complex closely resembles the PLN/SERCA1a complex, but with the luminal end of SLN extending to the loop connecting M1 and M2, where Tyr-29 and Tyr-31 interact with aromatic residues in SERCA1a. Modeling of the PLN/SLN/SERCA1a complex predicts that the regulator binding cavity in the E(2) conformation of SERCA1a can accommodate both SLN and PLN helices, but not two PLN helices.
机译：Phospholamban（PLN），肌（内）质网Ca（2 +）-ATPases（SERCAs）的调节剂，与胞质N结构域和SERCA的跨膜螺旋M2，M4，M6和M9相互作用。预测与SERCA1a相互作用的PLN跨膜结构域中的氨基酸在肌钙蛋白（SLN）（一种功能性PLN同源物）中保守。因此，比较了SERCA1a，PLN和NF-SLN（用FLAG表位在N端标记SLN）中的关键突变对NF-SLN / SERCA1a和PLN / NF-SLN / SERCA1a相互作用的影响。 SERCA1a和NF-SLN中的关键突变减少了SERCA1a和NF-SLN之间的功能相互作用，表明NF-SLN和PLN与SERCA1a中的某些相同氨基酸相互作用。 PLN或NF-SLN中的突变影响了在每种复合物中用抗PLN或SLN抗体共免疫沉淀的SERCA1a的量，但不影响共免疫沉淀的模式。与SLN突变相比，PLN突变对SERCA1a共免疫沉淀的影响更大，这表明PLN在与SERCA1a的主要相互作用中占主导地位。免疫共沉淀还证实PLN和NF-SLN形成异二聚体，以调节方式与SERCA1a相互作用形成非常稳定的PLN / NF-SLN / SERCA1a复合物。建模显示SLN / SERCA1a复合物非常类似于PLN / SERCA1a复合物，但SLN的腔末端延伸至连接M1和M2的环，其中Tyr-29和Tyr-31与SERCA1a中的芳香族残基相互作用。 PLN / SLN / SERCA1a复合体的模型预测，SERCA1a的E（2）构象中的调节子结合腔可以容纳SLN和PLN螺旋，但不能容纳两个PLN螺旋。

著录项

相似文献

  • 外文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号