Cross- 3 structure

A trademark of amyloid fibrils is their cross-/ structure. This structure is the basis of the repetitive hydrogen-bonding extension of the fibril (Makin et al., 2005). Cross-/ structures are observed in the silk fibers of some insects (Geddes et al., 1968 Hepburn et al., 1979), although none are observed in spiders or lepidoptera (Craig, 1997). This absence has been explained by the possibility that cross-/ silks or a-silks may be converted into collinear /1-silks by stretching the fiber and an increased orientation-function correlated to the speed at which silk is formed (Riekel et al., 2000). 

A better characterization of fibrils found in various silks could resolve this issue and most likely reveal the conformational criteria involved in the choice of the col I in ear-/) over the cross-/ structures. 

Cross-/] structure has been demonstrated for Sup35pNM filaments. Serio et al. (2000) observed a 0.47-nm reflection by X-ray diffraction, and subsequently this reflection was shown to be meridional both by X-ray fiber diffraction (Kishimoto et al., 2004) and electron diffraction (King and Diaz-Avalos, 2004). In the Ure2p system, cross-/ structure has been established by electron diffraction from prion domain filaments preserved in vitreous ice (Fig. 7 Baxa et al, 2005). In addition, a 0.47-nm reflection was detected by both X-ray diffraction and electron diffraction from filament preparations of full-length Ure2p and the Ure2p1 65-GFP fusion, indicating that they contain the same structure (Fig. 7 Baxa et al, 2005). 

We now summarize current experimentally derived constraints that models of yeast prion filaments must satisfy in addition to the basic requirement of cross-/) structure and then go on in Section VI to discuss their implications for several models that have been proposed. 

This model is a polar cross-/ structure with a left-handed twist that complies with the mass-per-unit-length data moreover, it readily accommodates sequence randomization because like residues are still stacked over like residues, regardless of their order, and sequence permutation does not increase the number of charged residues or prolines which would be most likely to destabilize structures of this kind (Fig. 10). The configuration of strands and turns allows some variation without putting charged residues inside the core structure. We envision that structural variations of this kind offer a plausible explanation for the phenomenon of prion variants, as discussed in Section VIII. 

Fig. 1. Cross-/] structure of amyloid fibrils. (A) Cartoon representation of a cross-/] X-ray diffraction pattern. The defining features are a meridional reflection at 4.7 A and an equatorial reflection on the order of 10 A. The 4.7-A reflection is generally much brighter and sharper than the reflection at 10 A. (B) The cross-/] core structure of amyloid fibrils. Parallel /(-sheets are depicted, but the structure could equivalendy be composed of antiparallel /(-sheets or a mix of parallel and antiparallel. The 4.7-A spacing of /(-strands within each /(-sheet is parallel to the long fibril axis. The depicted 10-A sheet-to-sheet spacing actually ranges from about 5 to 14 A (Fandrich and Dobson, 2002), depending on the size and packing of amino acid side chains. Amyloid fibrils have diameters on the order of 100 A.

Two models have been proposed for how this dimeric structure may relate to the structure of cystatin C in the fibril. The first (Janowski et at, 2001) proposes that run-away domain swapping (like that shown in Fig. 11C) can account for the assembly and stability of the fibril. In this model, one monomer would swap /(I-a 1-/12 into a second monomer, the second would swap its /(I-a 1-/12 into a third, and so on. The second model (Staniforth et al., 2001) proposes a direct stacking of domain-swapped dimers, where /i5 of each subunit of the dimer would interact with /(I of a subunit of the adjacent dimer. In this way, the dimers would stack to form continuous /1-sheets. Both models arrange the /(-sheets parallel to the fibril axis with component /(-strands perpendicular to the axis, as in a cross-/ structure, although no diffraction pattern has been reported for cystatin fibrils. 

Fay et al. (2005) have proposed a completely different model for Ure2p fibril structure. Their model is based on data which suggest that Ure2p fibrils do not have a cross-/ structure (Bousset et al., 2003) and that the C-terminal globular domain is tightly involved in the fibrillar scaffold (Bousset et al.,... 

Pt(II), and this cross structure has been supported by another X-ray analysis24 of ( )-2-cyclooctenyl-3, 5 -dinitrobenzoate as well as an electron diffraction study 25 of ( )-cyclooctene itself. Force-field calculations 26,1 have revealed that the race-mization of ( )-cyclooctene should follow the pathway (R)-cross 18-> (S)-chair 19 - (S)-cross 20, and that the former pathway is rate determining. 

Homologous strands are cleaved and rejoined to form crossed structure... 

The microwave spectrum of the complex between ethylene and ketene (and of deuter-ated derivatives) reveals56 a crossed structure (22), while the ketene/acetylene complex shows a planar geometry57. This difference in geometry is explained by the different quadrupole moments of two unsaturated hydrocarbons. 

Figure 7 Crystal structures and hydrogen-bonding networks of BHCA (a) bilayer structure, (b) crossing structure, and epibile acids with 2-pentanol, (c) 3EDCA, and (d) 3ECA.

Figure 9 Molecular packing diagrams of CA with (1) acrylonitrile (a) a crossing structure and (b) a bilayer structure with (2) methacrylonitrile (c) a crossing structure, and (d) a bilayer structure and (3) with ethyl acetate (e) Form I and (f) Form II. Hydrogen atoms are omitted for clarity. Carbon, nitrogen, and oxygen atoms are represented by open, gray and filled circles, respectively.

Figure 10 Crystal structures of CA with acetic acid (a) 1 1 crossing structure and (b) 1 2 bilayer structure. Crystal structures of CAM with acetonitrile and water (c) 1 1 1 triangular structure and (d) 1 1 2 bilayer structure. Open, gray and filled circles represent carbon, nitrogen and oxygen atoms, respectively. Hydrogen atoms are omitted for clarity.

---