Intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs) exist as interconverting conformational ensembles, without a single fixed three-dimensional structure in vivo. The focus in the literature up to this point has been primarily on IDPs that are mostly or entirely disordered. Therefore, we have an incomplete understanding of the incidence and functional relevance of IDPRs in proteins that have regions of both order and disorder. This work explores these populations, by examining IDPRs in the Protein Data Bank (PDB) and in enzymes. By applying disorder prediction methods combined with an analysis of missing regions in crystal structure data, this work shows that enzymes have a similar incidence and length of IDPRs as do non-enzymes, and that these IDPRs are correlated with functions related to macromolecular metabolism, signaling, and regulation. Furthermore, extensive analyses of missing regions with conflicting information between multiple structures in the PDB show that, rather than experimental artifacts, this ambiguity most likely arises due to partially or conditionally disordered regions. This work documents the first proteome level study of protein intrinsic disorder in enzyme populations and demonstrates a novel way of analyzing missing regions in the PDB. Furthermore, an extensive literature search as part of this work provides information for 1127 IDPs with experimental evidence documented in the literature, 96 of which are enzymes. The results contained herein present a new model of the protein universe, where disorder is directed by evolution in both non-enzymes and enzymes to make the most of limited proteomes in complex organisms through complicated signaling networks and tightly controlled regulation.
| Identifer | oai:union.ndltd.org:USF/oai:scholarcommons.usf.edu:etd-7415 |
| Date | 27 June 2016 |
| Creators | Deforte, Shelly |
| Publisher | Scholar Commons |
| Source Sets | University of South Flordia |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Graduate Theses and Dissertations |
| Rights | default |
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