Abstract
Many large-scale studies on intrinsically disordered proteins are implicitly based on the structural models deposited in the Protein Data Bank. Yet, the static nature of deposited models supplies little insight into variation of protein structure and function under diverse cellular and environmental conditions. While the computational predictability of disordered regions provides practical evidence that disorder is an intrinsic property of proteins, the robustness of disordered regions to changes in sequence or environmental conditions has not been systematically studied. We analyzed intrinsically disordered regions in the same or similar proteins crystallized independently and studied their sensitivity to changes in protein sequence and parameters of crystallographic experiments. The observed changes in the existence, position, and length of disordered regions indicate that their appearance in X-ray structures dramatically depends on changes in amino acid sequence and peculiarities of the crystallographic experiment. Our study also raises general questions regarding protein evolution and the regulation of protein structure, dynamics, and function via variations in cellular and environmental conditions.
Highlights
In the past decade, significant progress has been achieved in our understanding of the ubiquity and function of intrinsically disordered proteins [1,2,3,4,5,6,7,8]
Recent studies document the effects of varying environmental conditions on regions of intrinsic disorder in similar proteins
Disordered proteins are characterized by distinct amino acid preferences, distinct mechanisms of binding, distinct substitution patterns and rates of evolution, and functional roles predominantly related to signaling and regulation
Summary
Significant progress has been achieved in our understanding of the ubiquity and function of intrinsically disordered proteins [1,2,3,4,5,6,7,8]. We attempt to address these questions by investigating the variability of observed disordered regions with changes in sequence and environmental conditions used for crystallization. Recent studies document the effects of varying environmental conditions on regions of intrinsic disorder in similar proteins. Neither protein is compact in solution and possesses folded structure under physiological pH and temperature, P1a was found to be mostly disordered with low helical content, whereas P2b had significant residual structure. This residual structure disappeared at temperatures below 30uC, but was regained under low pH or in the presence of trifluoroethanol.
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