title: Proline Conformation in a Functional Tau Fragment.
abstract: The conformational state of distinct prolines can determine the folding of a protein but equally other biological processes when coupled to a conformation-sensitive secondary reaction. For the neuronal tau protein, the importance of proline conformation is underscored by its interaction with different prolyl cis/trans isomerases. The proline conformation would gain even further importance after phosphorylation of the preceding residue by various proline-directed kinases. A number of molecular diseases including Alzheimer's disease and traumatic brain injury were thereby recently qualified as "cistauosis", as they would imply a cis conformation for the pThr231-Pro232 prolyl bond. We here investigate by NMR spectroscopy the conformation of all prolines in a functional Tau fragment, Tau[208-324]. Although we can detect and identify some minor conformers in the cis form, we show that all prolines are for over 90% in the trans conformation. Phosphorylation by CDK2/CycA3, which notably leads to complete modification of the Thr231 residue, does not change this conclusion. Our data hence disagree with the notion that specific prolyl bonds in tau would adopt preferentially the cis conformation.
authors.affiliation: UMR8576 CNRS Lille University, 59658 Villeneuve d'Ascq, France.
authors.forename: Puneet
authors.initials: P
authors.lastname: Ahuja
authors.affiliation: UMR8576 CNRS Lille University, 59658 Villeneuve d'Ascq, France.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Cantrelle
authors.affiliation: UMR8576 CNRS Lille University, 59658 Villeneuve d'Ascq, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Huvent
authors.affiliation: UMR8576 CNRS Lille University, 59658 Villeneuve d'Ascq, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Hanoulle
authors.affiliation: UMR8576 CNRS Lille University, 59658 Villeneuve d'Ascq, France.
authors.forename: Juan
authors.initials: J
authors.lastname: Lopez
authors.affiliation: UMR8576 CNRS Lille University, 59658 Villeneuve d'Ascq, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Smet
authors.affiliation: UMR8576 CNRS Lille University, 59658 Villeneuve d'Ascq, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Wieruszeski
authors.affiliation: UMR8576 CNRS Lille University, 59658 Villeneuve d'Ascq, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Landrieu
authors.affiliation: UMR8576 CNRS Lille University, 59658 Villeneuve d'Ascq, France. Electronic address: Guy.Lippens@univ-lille1.fr.
authors.forename: G
authors.initials: G
authors.lastname: Lippens
mesh_terms: D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010766:Phosphorylation; D011392:Proline / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins; D011392:Proline
keywords: Tau protein; cis/trans isomerisation; exchange spectroscopy; nuclear magnetic resonance spectroscopy; proline conformation