title: The structure of the largest murine neurofilament protein (NF-H) as revealed by cDNA and genomic sequences.
abstract: The complete primary structure of the largest mammalian neurofilament component, NF-H, is predicted from mouse cDNA and genomic clones, revealing a protein of molecular weight ca. 115,000. A central filament-forming domain structurally typical of all intermediate filament proteins is present, but anomalies are noted which may place constraints on the mechanism of NF-H assembly into filaments. The COOH-terminal portion of the protein is extremely long (661 amino acids) by comparison to non-neuronal intermediate filament components and has a remarkably monotonous, highly charged composition (Glu and Lys at 20% each). Its most remarkable feature is a tandem repeat of a 6 amino acid sequence containing the motif Lys-Ser-Pro that extends for more than half the length of the COOH-terminus. The Lys-Ser-Pro motif appears 48 times and since it is now known that the serine therein is a target for in vivo kinases, the massive axonal phosphorylation of NF-H is explained. Comparison of mouse and human NF-H reveals that otherwise conserved proteins have been subjected to evolutionary mutation within their multiphosphorylation repeat domains, although the Lys-Ser-Pro motif has been conserved.
authors.affiliation: Laboratory of Molecular Genetics, National Institute of Neurological and Communicative Disorders and Stroke.
authors.forename: P S
authors.initials: PS
authors.lastname: Shneidman
authors.forename: M J
authors.initials: MJ
authors.lastname: Carden
authors.forename: J F
authors.initials: JF
authors.lastname: Lees
authors.forename: R A
authors.initials: RA
authors.lastname: Lazzarini
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000032:analysis* / Q000302:isolation & purification; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016900:Neurofilament Proteins; D012689:Sequence Homology, Nucleic Acid
chemical_list: D007381:Intermediate Filament Proteins; D016900:Neurofilament Proteins; D004247:DNA