Helical filaments

FIGURE 17. 33 A model of the flagellar motor assembly of Escherichia coli. The M ring carries an array of about 100 motB proteins at its periphery. These juxtapose with motA proteins in the protein complex that snrronnds the ring assembly. Motion of protons throngh the motA/motB complexes drives the rotation of the rings and the associated rod and helical filament. 

Monomeric G-actin (43 kDa G, globular) makes up 25% of muscle protein by weight. At physiologic ionic strength and in the presence of Mg, G-actin polymerizes noncovalently to form an insoluble double helical filament called F-actin (Figure 49-3). The F-actin fiber is 6-7 nm thick and has a pitch or repeating structure every 35.5 nm. 

Figure 18.1 Typical tangle (T) and plaque (P) as visualised by silver impregnation in the cerebral cortex of a case of Alzheimer s disease. The extracellular plaque (10-50 pm diameter) consists of a central core of amyloid surrounded by glial processes and a number of neurites in a ring formation. The intracellular cytoplasmic tangle is composed of helical filaments in a paired format. (Reproduced with permission of Academic Press from Wischik and Crowther 1986)...

Rather scanty evidence exists for the participation of free radicals in Alzheimer s disease and Down s syndrome. However, more recendy, reports have appeared that suggest possible free-radical involvement in the pathogenesis of these two conditions. Zemlan et al. (1989) repotted that the activity of the free-radical scavenging enzyme, SOD, was significantly increased in fibroblast cell lines derived from familial Alzheimer s and Down s patients. They hypothesized that the elevation in SOD activity observed in the Alzheimer patients supports the theory that paired helical filaments are formed by free-radical hydroxylation of proline residues. They further su ested that SOD levels might also be increased in the brains of Alzheimer s and Down s patients, and that the increase in SOD may reflect an enhanced generation of free radicals. 

Zemlan, F., Thienhaus, O.J. and Bosmann, H.B. (1989). Superoxide dismutase activity in Alzheimer s disease possible mechanism for paired helical filament formation. Brain Res. 476, 160-162. 

Schweers O, Schonbrann Hanebeck E, Marx A, Mandelkow E. Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for beta-structure. J Biol Chem 1994 269 24290-24297. 

FriedhoffP, Schneider A, Mandelkow EM, Mandelkow E. Rapid assembly of Alzheimer-like paired helical filaments from microtubule-associated protein tau monitored by flourescence in solution. Biochemistry 1998 37 10223-10230. 

Schweers O, Mandelkow EM, Biemat J, Mandelkow E. Oxidation of cysteine-322 in the repeat domain of microtubule-associated protein tau controls the in vitro assembly of paired helical filaments. Proc Natl Acad Sci USA 1995 92 8463-8467. 

The microvillar surface is coated with a layer of electron-dense amorphous material (glycocalyx). In H. contortus, helical filaments composed of contortin are associated with this layer and fill the spaces between the microvilli. There can be up to ten strands of contortin in each microvillus ... 

The paired helical filament is made of tau protein 753 Filamentous tau is hyperphosphorylated 753... 

Abundant neuritic plaques and neurofibrillary lesions define Alzheimer s disease. Plaques are extracellular deposits made of the fibrillar P-amyloid peptide. The paired helical filament (PHF) makes up the bulk of the intraneuronal neurofibrillary pathology of Alzheimer s disease, with the straight filament (SF) being a minority species. 

Goedert, M. et al. Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease Identification as the microtubule-associated protein tau. Proc. Natl. Acad. Sci. USA 85 4051-4055, 1988. 

Lee,V.M.-Y. etal. A68 a major subunit of paired helical filaments and derivatized forms of normal tau. Science 251 675-678, 1991. 

Von Bergen, M. etal. Assembly of tau protein into Alzheimer paired helical filaments depends on a local sequence motif [306QIVYK311] forming beta structure. Proc. Natl. Acad. Sci. USA 97 5129-5134, 2000. 

Figure 5.15 Dark-field optical micrograph of self-assembled helical filaments from an aqueous dispersion of 2Ci2-L-GluCnN+ (22) after aging for 30 h. Bar = 10 xm. Reprinted with permission from Ref. 74. Copyright 1985 by the American Chemical Society.

Kirschner, D. A., Abraham, C., and Selkoe, D. J. (1986). X-ray diffraction from intraneuronal paired helical filaments and extraneuronal amyloid fibers in Alzheimer disease indicates cross-beta conformation. Proc. Natl. Acad. Sci. USA 83, 503-507. 

Ksiezak-Reding, H., and Wall, J. S. (2005). Characterization of paired helical filaments by scanning transmission electron microscopy. Microsc. Res. Tech. 67, 126-140. 

How does the ubiquitin-proteasome pathway contribute to pathogenesis of AD. It is thought that the causative factors in AD, namely, the A/3 peptide, or the paired helical filaments (PHF) of tau protein, impair proteasome function. In in vitro experiments, A/3 peptide has been shown to inhibit the proteasome. In the brains of AD patients, proteasome function has been shown to be reduced mostly in the areas critical for... 

Pickhardt, M., Gazova, Z., von Bergen, M., et al. (2005) Anthraquinones inhibit tan aggregation and dissolve Alzheimer s paired helical filaments in vitro and in cells. J. Biol. Chem., 280, 3628-3635. 

There is also interest in the involvement of the cytoskeleton in such degenerative diseases as Alzheimer s disease (see Chapter 14) which is characterized by tangles (paired helical filaments). It seems likely that one of the microtubule-associated proteins (tau protein) is an important component of the tangles found in Alzheimer s disease. 

As illustrated in the diagram below, domain swapping can also result in indefinite polymerization to form linear supramolecular structures. These may correspond to present-day polymers of proteins such as microtubules, or they may represent abnormal structures, like the straight and paired-helical filaments in the neurofibrillary tangles observed in the brain tissue of those afflicted with Alzheimer s disease. 

Frost DWH, Yip CM, Chakrabartty A. Reversible assembly of helical filaments by de novo designed minimalist peptides. Biopolymers 2005 80 26-33. 

M. Uchida, T. Imahori, K. r protein kinase I converts normal tau protein into A68-like component of paired helical filaments. J. Biol. Chem., 267, 10897-10901 (1992)... 

ATP -I- T-protein = ADP -I- 0-phospho-T-protein (activated by tubulin. Different from EC 2.7.1.123 Ca /calmodulin-dependent protein kinase not activated by calmodulin, cyclic nucleotides or Ca. Involved in the formation of paired helical filaments in brain. See comment on EC 2.7.1.37 protein kinase)... 

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