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.
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