title: From the Cover: Charge interactions can dominate the dimensions of intrinsically disordered proteins.
abstract: Many eukaryotic proteins are disordered under physiological conditions, and fold into ordered structures only on binding to their cellular targets. Such intrinsically disordered proteins (IDPs) often contain a large fraction of charged amino acids. Here, we use single-molecule Förster resonance energy transfer to investigate the influence of charged residues on the dimensions of unfolded and intrinsically disordered proteins. We find that, in contrast to the compact unfolded conformations that have been observed for many proteins at low denaturant concentration, IDPs can exhibit a prominent expansion at low ionic strength that correlates with their net charge. Charge-balanced polypeptides, however, can exhibit an additional collapse at low ionic strength, as predicted by polyampholyte theory from the attraction between opposite charges in the chain. The pronounced effect of charges on the dimensions of unfolded proteins has important implications for the cellular functions of IDPs.
authors.affiliation: Biochemisches Institut, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors.forename: Sonja
authors.initials: S
authors.lastname: Müller-Späth
authors.forename: Andrea
authors.initials: A
authors.lastname: Soranno
authors.forename: Verena
authors.initials: V
authors.lastname: Hirschfeld
authors.forename: Hagen
authors.initials: H
authors.lastname: Hofmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Rüegger
authors.forename: Luc
authors.initials: L
authors.lastname: Reymond
authors.forename: Daniel
authors.initials: D
authors.lastname: Nettels
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schuler
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020124:Thermotoga maritima / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D011506:Proteins; D003545:Cysteine