title: Assigning backbone NMR resonances for full length tau isoforms: efficient compromise between manual assignments and reduced dimensionality.
abstract: Tau protein is the longest disordered protein for which nearly complete backbone NMR resonance assignments have been reported. Full-length tau protein was initially assigned using a laborious combination of bootstrapping assignments from shorter tau fragments and conventional triple resonance NMR experiments. Subsequently it was reported that assignments of comparable quality could be obtained in a fully automated fashion from data obtained using reduced dimensionality NMR (RDNMR) experiments employing a large number of indirect dimensions. Although the latter strategy offers many advantages, it presents some difficulties if manual intervention, confirmation, or correction of the assignments is desirable, as may often be the case for long disordered and degenerate polypeptide sequences. Here we demonstrate that nearly complete backbone resonance assignments for full-length tau isoforms can be obtained without resorting either to bootstrapping from smaller fragments or to very high dimensionality experiments and automation. Instead, a set of RDNMR triple resonance experiments of modest dimensionality lend themselves readily to efficient and unambiguous manual assignments. An analysis of the backbone chemical shifts obtained in this fashion indicates several regions in full length tau with a notable propensity for helical or strand-like structure that are in good agreement with previous observations.
authors.affiliation: Tri-Institutional Program in Chemical Biology, Department of Biochemistry, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Harbison
authors.forename: Shibani
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: David
authors.initials: D
authors.lastname: Eliezer
mesh_terms: D000595:Amino Acid Sequence; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D020033:Protein Isoforms / Q000737:chemistry; D016875:tau Proteins / Q000737:chemistry*
chemical_list: D020033:Protein Isoforms; D016875:tau Proteins