Resolving the Ambiguity: Making Sense of Intrinsic Disorder When PDB Structures Disagree
Document Type
Article
Publication Date
2016
Keywords
protein data bank, PDB, intrinsically disordered protein, intrinsically disordered protein region, disorder prediction, missing residues, X-ray crystallography
Digital Object Identifier (DOI)
https://doi.org/10.1002/pro.2864
Abstract
Missing regions in X-ray crystal structures in the Protein Data Bank (PDB) have played a foundational role in the study of intrinsically disordered protein regions (IDPRs), especially in the development of in silico predictors of intrinsic disorder. However, a missing region is only a weak indication of intrinsic disorder, and this uncertainty is compounded by the presence of ambiguous regions, where more than one structure of the same protein sequence “disagrees” in terms of the presence or absence of missing residues. The question is this: are these ambiguous regions intrinsically disordered, or are they the result of static disorder that arises from experimental conditions, ensembles of structures, or domain wobbling? A novel way of looking at ambiguous regions in terms of the pattern between multiple PDB structures has been demonstrated. It was found that the propensity for intrinsic disorder increases as the level of ambiguity decreases. However, it is also shown that ambiguity is more likely to occur as the protein region is placed within different environmental conditions, and even the most ambiguous regions as a set display compositional bias that suggests flexibility. The results suggested that ambiguity is a natural result for many IDPRs crystallized under different conditions and that static disorder and wobbling domains are relatively rare. Instead, it is more likely that ambiguity arises because many of these regions were conditionally or partially disordered.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Protein Science, v. 25, issue 3, p. 676-688
Scholar Commons Citation
DeForte, Shelly and Uversky, Vladimir N., "Resolving the Ambiguity: Making Sense of Intrinsic Disorder When PDB Structures Disagree" (2016). Molecular Medicine Faculty Publications. 341.
https://digitalcommons.usf.edu/mme_facpub/341
