Dataset Information

Phosphorylation Increases Persistence Length and End-to-End Distance of a Segment of Tau Protein.

ABSTRACT: Intrinsically disordered regions of proteins, which lack unique tertiary structure under physiological conditions, are enriched in phosphorylation sites and in significant local bias toward the polyproline II conformation. The overrepresented coincidence of this posttranslational regulatory signal and local conformational bias within unstructured regions raises a question: can phosphorylation serve to manipulate the conformational preferences of a disordered protein? In this study, we use time-resolved fluorescence resonance energy transfer and a, to our knowledge, novel data analysis method to directly measure the end-to-end distance distribution of a phosphorylatable peptide derived from the human microtubule associated protein tau. Our results show that phosphorylation at threonine or serine extends the end-to-end distance and increases the effective persistence length of the tested model peptides. Unexpectedly, the extension is independent of salt concentration, suggestive of a nonelectrostatic origin. The phosphorylation extension and stiffening effect provides a peptide-scale physical interpretation for the posttranslational regulation of the highly abundant protein-protein interactions found in disordered proteins, as well as a potential insight into the regulatory mechanism of the tau protein's microtubule binding activity.

SUBMITTER: Chin AF

PROVIDER: S-EPMC4725354 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Phosphorylation Increases Persistence Length and End-to-End Distance of a Segment of Tau Protein.

Chin Alexander F AF Toptygin Dmitri D Elam W Austin WA Schrank Travis P TP Hilser Vincent J VJ

Biophysical journal 20160101 2

Intrinsically disordered regions of proteins, which lack unique tertiary structure under physiological conditions, are enriched in phosphorylation sites and in significant local bias toward the polyproline II conformation. The overrepresented coincidence of this posttranslational regulatory signal and local conformational bias within unstructured regions raises a question: can phosphorylation serve to manipulate the conformational preferences of a disordered protein? In this study, we use time-r ...[more]

PMID: 26789759

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Project description:BACKGROUND: Many studies have examined rules governing two aspects of protein structures: short segments and proteins' structural domains. Nevertheless, the organization and nature of the conformational space of segments with intermediate length between short segments and domains remain unclear. Conformational spaces of intermediate length segments probably differ from those of short segments. We investigated the identification and characterization of the boundary(s) between peptide-like (short segment) and protein-like (long segment) distributions. We generated ensembles embedded in globular proteins comprising segments 10-50 residues long. We explored the relationships between the conformational distribution of segments and their lengths, and also protein structural classes using principal component analysis based on the intra-segment Calpha-Calpha atomic distances. RESULTS: Our statistical analyses of segment conformations and length revealed critical dual transitions in their conformational distribution with segments derived from all four structural classes. Dual transitions were identified with the intermediate phase between the short segments and domains. Consequently, protein segment universes were categorized. i) Short segments (10-22 residues) showed a distribution with a high frequency of secondary structure clusters. ii) Medium segments (23-26 residues) showed a distribution corresponding to an intermediate state of transitions. iii) Long segments (27-50 residues) showed a distribution converging on one huge cluster containing compact conformations with a smaller radius of gyration. This distribution reflects the protein structures' organization and protein domains' origin. Three major conformational components (radius of gyration, structural symmetry with respect to the N-terminal and C-terminal halves, and single-turn/two-turn structure) well define most of the segment universes. Furthermore, we identified several conformational components that were unique to each structural class. Those characteristics suggest that protein segment conformation is described by compositions of the three common structural variables with large contributions and specific structural variables with small contributions. CONCLUSION: The present results of the analyses of four protein structural classes show the universal role of three major components as segment conformational descriptors. The obtained perspectives of distribution changes related to the segment lengths using the three key components suggest both the adequacy and the possibility of further progress on the prediction strategies used in the recent de novo structure-prediction methods.

Dataset Information

Phosphorylation Increases Persistence Length and End-to-End Distance of a Segment of Tau Protein.

Publications

Phosphorylation Increases Persistence Length and End-to-End Distance of a Segment of Tau Protein.

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