FAST FOLDING EVENTS IN TPR PROTEINS

TPR 蛋白质中的快速折叠事件

• 批准号: 7373145
• 负责人: LYNNE J. REGAN
• 金额: $ 0.34万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7373145
• 关键词: FAST; FOLDING; EVENTS; TPR; PROTEINS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. One critical step in the ?-helical protein folding is helices packing: how the elementary secondary structures form the native tertiary structure through various and distinct packing styles, which differ from parallel packing in coiled-coils to almost perpendicular packing in hemoglobin. One of the specific structural motifs of interest is the tetratrico peptide repeat (TPR), which occurs in many classes of proteins, and mediates protein-protein interactions and the assembly of multiprotein complexes. Proteins containing TPRs are involved in many biological processes, such as cell cycle regulation, transcriptional control, mitochondrial and peroxisomal protein transport, neutogenesis and protein folding. The X-ray study of a domain with three TPRs from protein phosphatase 5 showed that TPR adopts helix-turn-helix structure, with adjacent TPR motifs in parallel fashion, resulting in a spiral of antiparallel ?-helices. The two ?-helices within a single TPR motif have a packing angle around 24 degree and form a right-handed superhelical shape. Our interest in the TPR motifs stems not only from their significant biological functions, but also from their unique molecular architecture and folding characteristics. The investigation of folding mechanisms of TPR proteins will provide better understanding of helix-helix interaction as well as folding mechanisms of ?-helical proteins with different packing features. Preliminary thermodynamic and kinetic study has been done on an individual TPR which also contains a stabilizing N-cap sequence and a solvating helix at C-teminal to enhance the solubility. CD experiments demonstrated this TPR has a cooperative two-state thermal transition. And two-state folding kinetics were also observed with the laser induced temperature jump experiments.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。 ？ - 螺旋蛋白折叠的一个关键步骤是螺旋堆积：基本二级结构如何通过各种且独特的堆积样式形成天然的三级结构，这不同于在盘绕螺旋中的平行包装到血红蛋白中几乎垂直的堆积。感兴趣的特定结构基序之一是四类肽重复（TPR），它发生在许多类别的蛋白质中，并介导蛋白质 - 蛋白质相互作用和多蛋白复合物的组装。含有TPR的蛋白质参与了许多生物学过程，例如细胞周期调节，转录控制，线粒体和过氧化物酶体蛋白转运，中孕和蛋白质折叠。对蛋白质磷酸酶5的三个TPR的结构域进行的X射线研究表明，TPR采用螺旋 - 旋转螺旋结构，并以平行方式具有相邻的TPR基序，从而产生了抗皮平行的螺旋。单个TPR基序中的两个螺旋在24度左右的填料角度，形成右手的超螺旋形状。我们对TPR主题的兴趣不仅源于它们的重要生物学功能，还源于其独特的分子结构和折叠特征。对TPR蛋白的折叠机制的研究将更好地理解螺旋 - 螺旋相互作用以及具有不同包装特征的螺旋蛋白的折叠机制。初步的热力学和动力学研究是在单个TPR上进行的，该研究还包含稳定的N-CAP序列和在C-心理中的溶剂化螺旋，以增强溶解度。 CD实验表明该TPR具有合作的两态热转变。在激光诱导的温度跳跃实验中，还观察到了两态折叠动力学。