• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >High-resolution structural analysis of mammalian profilin 2a complex formation with two physiological ligands: The formin homology 1 domain of mDial and the proline-rich domain of VASP
【24h】

High-resolution structural analysis of mammalian profilin 2a complex formation with two physiological ligands: The formin homology 1 domain of mDial and the proline-rich domain of VASP

机译：具有两个生理配体的哺乳动物profilin 2a复合物形成的高分辨率结构分析：mDial的formin同源性1域和VASP的富含脯氨酸的域

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

Profilins are small proteins capable of binding actin, poly-L-proline and other proline-rich sequences, and phosphatidylinositol (4,5)-bisphosphate. A number of proline-rich ligands for profilin have been characterised, including proteins of the Ena/VASP and formin families. We have determined the high-resolution crystal structures of mouse profilin 2a in complex with peptides from two functionally important ligands from different families, VASP and mDia1. The structures show that the binding mode of the peptide ligand is strongly affected by the non-proline residues in the sequence, and the peptides from VASP and mDia1 bind to profilin 2a in distinct modes. The high resolution of the crystallographic data allowed us to detect conserved CH-pi hydrogen bonds between the peptide and profilin in. both complexes. Furthermore, both peptides, which are shown to have micromolar affinity, induced the dimerisation of profilin, potentially leading to functionally different ligand-profilin-actin complexes. The peptides did not significantly affect actin polymerisation kinetics in the presence or in the absence of profilin 2a. Mutant profilins were tested for binding to poly-L-proline and the VASP and mDial peptides, and the F139A mutant bound proline-rich ligands with near-native affinity. Peptide blotting using a series of designed peptides with profilins 1 and 2a indicates differences between the two profilins towards proline-rich peptides from mDial and VASP. Our data provide structural insights into the mechanisms of mDial and VASP regulated actin polymerisation. (c) 2007 Elsevier Ltd. All rights reserved.
机译：脯氨酸蛋白是能够结合肌动蛋白，聚-L-脯氨酸和其他富含脯氨酸的序列以及磷脂酰肌醇（4,5）-双磷酸酯的小蛋白质。已经鉴定了许多脯氨酸蛋白的富含脯氨酸的配体，包括Ena / VASP和formin家族的蛋白。我们已经确定了小鼠血浆蛋白2a的高分辨率晶体结构与来自不同家族的两个功能重要配体VASP和mDia1的肽复合。该结构表明，肽配体的结合模式受序列中非脯氨酸残基的强烈影响，并且来自VASP和mDia1的肽以不同的模式结合至脯氨酸蛋白2a。晶体学数据的高分辨率使我们能够检测到两种复合物中肽和脯氨酸蛋白之间的保守CH-pi氢键。此外，显示具有微摩尔亲和力的两种肽均诱导了profilin的二聚化，潜在地导致功能上不同的配体-profilin-肌动蛋白复合物。在存在或不存在profilin 2a的情况下，这些肽均不会显着影响肌动蛋白的聚合动力学。测试了突变蛋白原与聚-L-脯氨酸以及VASP和mDial肽的结合，并且F139A突变体以接近天然的亲和力结合了富含脯氨酸的配体。使用一系列设计的具有蛋白纤溶酶1和2a的肽进行的肽印迹表明，这两个蛋白纤溶酶与mDial和VASP中富含脯氨酸的肽之间存在差异。我们的数据提供了对mDial和VASP调控的肌动蛋白聚合机制的结构见解。 （c）2007 Elsevier Ltd.保留所有权利。

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