Metal ion-induced conformational changes of phosphorylated fragments of human neurofilament (NF-M) protein.
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.
Hollósi
M
M
Institute of Organic Chemistry, L. Eötvös University, Budapest, Hungary.
Urge
L
L
Perczel
A
A
Kajtár
J
J
Teplán
I
I
Otvös
L
L
Fasman
G D
GD
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
D016900:Neurofilament Proteins; D010750:Phosphoproteins; C061195:neurofilament protein M; D000535:Aluminum; D002118:Calcium