title: Metal ion-induced conformational changes of phosphorylated fragments of human neurofilament (NF-M) protein.
abstract: The NF-M subunit of human neurofilaments has a C-terminal repeating 13-mer sequence. The 13-mer (Lys-Ser-Pro-Val-Pro-Lys-Ser-Pro-Val-Glu-Glu-Lys-Gly) (NF-M13) and 17-mer (Glu-Glu-Lys-Gly)-(NF-M13) sequences were synthesized, as were both the mono- and diphosphorylated Ser species. Circular dichroism (c.d.) studies and c.d. titrations with Al3+ and Ca2+ were performed. The conformation of the phosphorylated and unphosphorylated material was random in water. Deconvolution of the c.d. spectra, in trifluoroethanol, of the untitrated samples yielded a high content of unordered structure, similar to the poly-L-proline II structure. Titration of the phosphorylated species with Al3+ or Ca2+ caused a surprising conformational change to occur, yielding a high content of beta-pleated sheet structure. A mechanism of metal binding to the phosphofragments is proposed which may be relevant to the formation of neurofibrillary tangles in Alzheimer's disease.
authors.affiliation: Institute of Organic Chemistry, L. Eötvös University, Budapest, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Hollósi
authors.forename: L
authors.initials: L
authors.lastname: Urge
authors.forename: A
authors.initials: A
authors.lastname: Perczel
authors.forename: J
authors.initials: J
authors.lastname: Kajtár
authors.forename: I
authors.initials: I
authors.lastname: Teplán
authors.forename: L
authors.initials: L
authors.lastname: Otvös
authors.forename: G D
authors.initials: GD
authors.lastname: Fasman
mesh_terms: D000535:Aluminum / Q000737:chemistry*; D000595:Amino Acid Sequence; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry*; D002942:Circular Dichroism; D006801:Humans; D008969:Molecular Sequence Data; D016900:Neurofilament Proteins / Q000737:chemistry*; D010750:Phosphoproteins / Q000737:chemistry; D010766:Phosphorylation; D011487:Protein Conformation
chemical_list: D016900:Neurofilament Proteins; D010750:Phosphoproteins; C061195:neurofilament protein M; D000535:Aluminum; D002118:Calcium