Fibril assembly

Van Nostrand WE, Melchor JP, Ruffini L. Pathologic amyloid beta-protein cell surface fibril assembly on cultured human cerebrovascular smooth muscle cells. J Neurochem 1998 70 216-223. 

IV. Depicting Intermediate Stages of Amyloid Fibril Assembly.. . 223... 

A comparable folding mechanism was found in silks. A seminal study by Li et al. (2001) found that in vitro formation of silk fibrils is conformation dependent and occurred via a nucleation mechanism. Although now established as amyloidogenic (Kenney et al., 2002), the nature of the silk fibril assembly remains unclear. Noteworthy is the evidence for a cross-nucleation ability of silk proteins, supporting the amyloidogenicity of silk (Lundmark et al., 2005). 

Bousset, L., Briki, F., Doucet, J., and Melki, R. (2003). The native-like conformation of Ure2p in fibrils assembled under physiologically relevant conditions switches to an amyloid-like conformation upon heat-treatment of the fibrils. /. Struct. Biol. 141, 132-142. 

AMYLOID FIBRIL ASSEMBLY PATHWAYS AND CYTOTOXICITY MECHANISMS... 

In this chapter, we first describe amyloid fibril polymorphism as seen by EM. We then show how SFM was used to depict intermediate stages of amyloid fibril assembly. Finally, we discuss the putative mechanism that might explain the cytotoxicity induced by these assembly intermediates. 

Amylin fibrils growing on mica were rather straight and exhibited various heights. They were compatible with the protofibril hypothesis of amyloid fibril polymorphism (Fig. 3), but no multistranded cables were present (Goldsbury et al, 1999). In contrast, coiled fibrils were often observed by SFM for fibrils assembled in solution prior to being adsorbed to mica (Jansen et al, 2005 Kad et al, 2003 Relini et al, 2004). In the case of... 

This enzyme [EC 3.4.24.14], also known as procollagen A-proteinase, catalyzes the hydrolysis of the A-propep-tide of the collagen chain a-l(l) at Pro—Gin and of a-2(11) chain at Ala—Gin. As a result, A-terminal propeptides of type I and II collagens are released prior to fibril assembly. However, it does not act on type III procollagen. 

Since fibril assembly can be regarded in part as a spontaneous self-assembly process, the limitation of fibril size could be ascribed to a physical equilibrium between soluble procollagen molecules and the growing insoluble fibril. Fibril-forming collagens are synthesized as precursor... 

Birk, D. E. (2001). Type V collagen Heterotypic type I/V collagen interactions in the regulation of fibril assembly. Micron 32, 223-237. 

Lumican regulates collagen fibril assembly Skin fragility and corneal opacity in the absence of lumican./. Cell Biol. 141, 1277-1286. 

This chapter describes the self-assembly of non-native protein fibers known as amyloid fibrils and the development of these fibrils for potential applications in nanotechnology and biomedicine. It extends an earlier review by the author on a related topic (Gras, 2007). In Section 1, the self-assembly of polypeptides into amyloid fibrils and efforts to control assembly and any subsequent disassembly are discussed. In Section 2, this review focuses on the important role of surfaces and interfaces during and after polypeptide assembly. It examines how different surfaces can influence fibril assembly, how surfaces can be used to direct self-assembly in order to create highly ordered structures, and how different techniques can be used to create aligned and patterned materials on surfaces following self-assembly. 

A number of techniques can be used to monitor the growth of amyloid fibrils and provide information on the kinetics of fibril assembly or disassembly. These techniques include light scattering or dye binding assays where Thioflavin T binds to the emerging fibril structure resulting in an increase in fluorescence (Krebs et al., 2005). Fourier transform infrared spectroscopy and circular dichroism can be used to monitor a change in secondary structure as the polypeptide adopts a (3-sheet-rich confirmation (Nilsson, 2004) and a quartz crystal oscillator used to follow an increase in fibril mass as a function of time (Knowles et al., 2007). 

Seeding is one way of potentially controlling what is typically an uncontrolled fibril assembly process, where polypeptide building blocks are combined in solution under favorable conditions. Seeds are short fibril fragments that can nucleate fibril growth, eliminate the lag phase, and... 

A surface or interface can influence the assembly of fibrils by altering both the process and kinetics of fibril nucleation or elongation. This behavior is not surprising as surface properties are known to influence the absorption, confirmation, and destabilization of globular proteins or smaller peptides (Rocha et al., 2005). Surface properties influence fibril assembly in a similar way by altering the absorption, unfolding, and aggregation of monomers. 

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