• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 1
  • Tagged with
  • 2
  • 2
  • 2
  • 2
  • 2
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Investigation of Respiratory Syncytial Virus Structural Determinants and Exploitation of the Host Ubiquitin System

Whelan, Jillian Nicole 07 April 2016 (has links)
Respiratory syncytial virus (RSV) is a globally circulating, non-segmented, negative sense (NNS) RNA virus that causes severe lower respiratory infections. This study explored several avenues to ultimately expand upon our understanding of RSV pathogenesis at the protein level. Evaluation of RSV intrinsic protein disorder increased the relatively limited description of the RSV structure-function relationship. Global proteomics analysis provided direction for further hypothesis-driven investigation of host pathways altered by RSV infection, specifically the interaction between the RSV NS2 protein and the host ubiquitin system. NS2 primarily acts to antagonize the innate immune system by targeting STAT2 for proteasomal degradation. The goal was to identify NS2 residues important for interaction with the host ubiquitin system, as well as describe the mechanism by which NS2 induces host protein ubiquitination. Bioinformatics analysis provided a platform for development of loss-of-ubiquitin-function NS2 mutants. Combining critical mutations as double or triple NS2 ubiquitin mutants displayed an additive effect on reducing NS2-induced ubiquitination. Recombinant RSV (rRSV) containing NS2 ubiquitin mutations maintained their effect on ubiquitin expression during infection in addition to limiting STAT2 degradation activity. NS2 ubiquitin mutants decreased rRSV growth and increased levels of innate immune responses, indicating a correlation between NS2’s ubiquitin function and antagonism of type I IFN to enhance viral replication. Finally, several proteomics strategies were employed to identify specific cellular proteins ubiquitinated by NS2 to further define host-pathogen interactions during RSV infection. This study demonstrates an effective approach for limiting viral protein function to enhance immune responses during infection.
2

MoRFs A Dataset of Molecular Recognition Features

Mohan, Amrita 26 July 2006 (has links)
Submitted to the faculty of the Bioinformatics Graduate Program in partial fulfillment of the requirements for the degree Master of Science in the School of Informatics, Indiana University December 2005 / The last decade has witnessed numerous proteomic studies which have predicted and successfully confirmed the existence of extended structurally flexible regions in protein molecules. Parallel to these advancements, the last five years of structural bioinformatics has also experienced an explosion of results on molecular recognition and its importance in protein-protein interactions. This work provides an extension to past and ongoing research efforts by looking specifically at the “flexibility and disorder†found in protein sequences involved in molecular recognition processes and known as, Molecular Recognition Elements or Molecular Recognition Features (MoREs or MoRFs, as we call them). MoRFs are relatively short in length (10 – 70 residues length); loosely structured protein regions within longer sequences that are largely disordered in nature. Interestingly, upon binding to other proteins, these MoRFs are able to undergo disorder-to-order transition. Thus, in our interpretation, MoRFs could serve as potential binding sites, and that this binding to another protein lends a functional advantage to the whole protein complex by enabling interaction with their physiological partner. There are at least three basic types of MoRFs: those that form α-helical structures upon binding, those that form β-strands (in which the peptide forms a β-sheet with additional β-strands provided by the protein partner), and those that form irregular structures when bound. Our proposed names for these structures are α-MoRF (also known as α-MoRE, alpha helical molecular recognition feature/element), β-MoRF (beta sheet molecular recognition feature/element), and I-MoRF (Irregular molecular recognition feature/element), respectively. The results presented in this work suggest that functionally significant residual structure can exist in MoRF regions prior to the actual binding event. We also demonstrate profound conformational preferences within MoRF regions for α-helices. We believe that the results from this study would subsequently improve our understanding of protein-protein interactions especially those related to the molecular recognition, and may pave way for future work on the development of protein binding site predictions. We hope that via the conclusions of this work, we would have demonstrated that within only a few of years of its conception, intrinsic protein disorder has gained wide-scale importance in the field of protein-protein interactions and can be strongly associated with molecular recognition.

Page generated in 0.1115 seconds