INTERACTION OF DNAK WITH APOMB

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 研究了共翻译活性伴侣蛋白Hsp70在调节多肽构象和折叠中的作用。调查主要通过多维核磁共振进行，以揭示高分辨率信息。在活细胞中，动力学论证表明，在完成全长多肽链的合成之前，有充足的时间进行构象采样以进行共翻译。蛋白质合成的载体性质和复杂的细胞环境可能会影响从头蛋白质的折叠。因此，重要的是要确定蛋白质在细胞内是如何折叠的。已知分子伴侣在蛋白质合成过程中与新生的核糖体结合多肽链相互作用。然而，目前尚不清楚它们对多肽构象的影响程度，以及它们是否能够重塑共翻译和翻译后立即折叠的景观。目前的工作专门针对这一问题。在包含共翻译活性Hsp70分子伴侣的底物结合域及其多肽底物的体外模型体系中，研究了复合体的形成对多肽构象的影响。讨论了底物结合域在多肽结合时的变化，以及底物构象对伴侣结合的调节。这项研究在残基水平上提供了与涉及Hsp70伴侣的复杂形成相关的构象变化的见解。

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. The role of the cotranslationally active chaperone Hsp70 in modulating polypeptide conformation and folding is studied. Investigations are primarily carried out by multidimensional nuclear magnetic resonance to reveal high-resolution information. In living cells, kinetic arguments indicate that there is ample time for conformational sampling to take place cotranslationally, before synthesis of the full-length polypeptide chain has been completed. The vectorial nature of protein synthesis and the complex cellular environment potentially affect de novo protein folding. It is therefore important to characterize how proteins fold in the cellular context. Molecular chaperones are known to interact with nascent ribosome-bound polypeptide chains during protein synthesis. However, it is not known to what extent they affect polypeptide conformation, and whether or not they are able to reshape the cotranslational and immediately post-translational folding landscapes. The current work specifically addresses this issue. The effect of complex formation on polypeptide conformation is investigated in an in vitro model system comprising the substrate binding domain of the cotranslationally active Hsp70 chaperone and its peptide substrates. The changes in the substrate binding domain upon peptide binding, as well as the modulation of substrate conformation upon chaperone-binding are addressed. The study provides insights at the residue level on the conformational changes associated with complex formation involving the Hsp70 chaperone.