Temperature-dependent structural changes in intrinsically disordered proteins: formation of alpha-helices or loss of polyproline II?
Structural characterization of intrinsically disordered proteins (IDPs) is mandatory for deciphering their potential unique physical and biological properties. A large number of circular dichroism (CD) studies have demonstrated that a structural change takes place in IDPs with increasing temperature, which most likely reflects formation of transient alpha-helices or loss of polyproline II (PPII) content. Using three IDPs, ACTR, NHE1, and Spd1, we show that the temperature-induced structural change is common among IDPs and is accompanied by a contraction of the conformational ensemble. This phenomenon was explored at residue resolution by multidimensional NMR spectroscopy. Intrinsic chemical shift referencing allowed us to identify regions of transiently formed helices and their temperature-dependent changes in helicity. All helical regions were found to lose rather than gain helical structures with increasing temperature, and accordingly these were not responsible for the change in the CD spectra. In contrast, the nonhelical regions exhibited a general temperature-dependent structural change that was independent of long-range interactions. The temperature-dependent CD spectroscopic signature of IDPs that has been amply documented can be rationalized to represent redistribution of the statistical coil involving a general loss of PPII conformations.
Kjaergaard
Magnus
M
Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Copenhagen N DK-2200, Denmark.
Nørholm
Ann-Beth
AB
Hendus-Altenburger
Ruth
R
Pedersen
Stine F
SF
Poulsen
Flemming M
FM
Kragelund
Birthe B
BB
D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics; D002942:Circular Dichroism; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D053838:Scattering, Small Angle; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry / Q000235:genetics; D013696:Temperature
D027682:Cation Transport Proteins; D005656:Fungal Proteins; D010455:Peptides; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; C011083:polyproline