title: Time, space, and disorder in the expanding proteome universe.
abstract: 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.
authors.affiliation: Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK.|Cambridge Centre for Proteomics, Department of Biochemistry, University of Cambridge, Cambridge, UK.|Department of Biochemistry, University of Cambridge, Cambridge, UK.
authors.forename: David-Paul
authors.initials: DP
authors.lastname: Minde
authors.affiliation: Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: A Keith
authors.initials: AK
authors.lastname: Dunker
authors.affiliation: Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK.|Cambridge Centre for Proteomics, Department of Biochemistry, University of Cambridge, Cambridge, UK.|Department of Biochemistry, University of Cambridge, Cambridge, UK.
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Lilley
mesh_terms: D017398:Alternative Splicing; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D019175:DNA Methylation; D015894:Genome, Human; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000295:instrumentation / Q000379:methods*; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D062211:Spatio-Temporal Analysis; D013997:Time Factors
chemical_list: D064267:Intrinsically Disordered Proteins; D020543:Proteome; D022661:RNA, Untranslated
keywords: Alternative splicing; Conformation; Intrinsically disordered protein; Membrane proteins; Post-translational modification