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 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。 α-螺旋蛋白质折叠中的一个关键步骤是螺旋堆积：基本二级结构如何通过各种不同的堆积方式形成天然三级结构，这些方式不同于卷曲螺旋中的平行堆积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肽重复序列 (TPR)，它出现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质复合物的组装。含有 TPR 的蛋白质参与许多生物过程，例如细胞周期调节、转录控制、线粒体和过氧化物酶体蛋白质运输、神经发生和蛋白质折叠。对来自蛋白磷酸酶5的具有三个TPR的结构域的X射线研究表明，TPR采用螺旋-转角-螺旋结构，相邻的TPR基序以平行方式形成，从而形成反平行α螺旋的螺旋。单个 TPR 基序内的两个 β 螺旋具有约 24 度的堆积角，并形成右手超螺旋形状。我们对 TPR 基序的兴趣不仅源于其重要的生物学功能，还源于其独特的分子结构和折叠特征。 TPR蛋白折叠机制的研究将有助于更好地理解螺旋-螺旋相互作用以及具有不同包装特征的β-螺旋蛋白的折叠机制。对单个 TPR 进行了初步热力学和动力学研究，该 TPR 还包含稳定的 N 帽序列和 C 末端的溶剂化螺旋以增强溶解度。 CD 实验证明该 TPR 具有协同的两态热转变。通过激光诱导温跃实验还观察到了二态折叠动力学。