Time, space, and disorder in the expanding proteome universe

Proteins are highly dynamic entities. Their myriad functions require specific structures, but proteins’ dynamic nature ranges all the way from the local mobility of their amino acid constituents to mobility within and well beyond single cells. A truly comprehensive view of the dynamic structural proteome includes: (i) alternative sequences, (ii) alternative conformations, (iii) alternative interactions with a range of biomolecules, (iv) cellular localizations, (v) alternative behaviors in different cell types. While these aspects have traditionally been explored one protein at a time, we highlight recently emerging global approaches that accelerate comprehensive insights into these facets of the dynamic nature of protein structure. Computational tools that integrate and expand on multiple orthogonal data types promise to enable the transition from a disjointed list of static snapshots to a structurally explicit understanding of the dynamics of cellular mechanisms.D.P.M. is funded by BBSRC grant BB/N010493/1

High-performance deep-ultraviolet optics for free-electron lasers

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Differential subnuclear localisation of hnRNPs A/B is dependent on transcription and cell cycle stage

The heterogeneous nuclear ribonucleoproteins A1, A2/B1 and A3 (hnRNPs A/B) are involved in many nuclear functions that are confined to distinct regions within the nucleus. To characterise and compare the distribution of the hnRNPs A/B in these subnuclear compartments, their colocalisation with spliceosomal components, nascent transcripts and other nuclear markers in HeLa cells was investigated by immunostaining and transfection of GFP constructs. The mechanisms of this localisation were further explored by treating cells with detergent, nucleases and transcription inhibitors. We have also examined the dynamics of A2/B1 throughout the cell cycle. Our results show that hnRNPs A/B have different subnuclear localisations, with A1 differentially localised to the nuclear envelope, and A2/B1 and A3 enriched around nucleoli. This pattern of distribution was dependent on RNA integrity and active transcription. The hnRNPs A/B preferentially colocalised with a subset of splicing factors. Significantly, only rarely did transcription factories colocalise with high levels of these hnRNPs. Moreover, localisation of A2/B1 changed with cell cycle stage. Our findings show that the subnuclear localisation of the hnRNPs A/B is differentially, spatially and temporally regulated, and suggest that this localisation may be relevant to their nuclear functions