Folding patterns

Polymer chain ends disrupt the orderly fold pattern of the crystal and tend to be excluded from the crystal and relegated to the amorphous portion of the sample. 

McLachlan, A.D. Repeated folding pattern in copper-zinc superoxide dismutase. Nature 285 267-268, 1980. 

Cowan, S.W., Rosenbusch, J.R Folding pattern diversity of integral membrane proteins. Science 264 914-916, 1994. 

FIGURE 12.39 The proposed secondary structure for E. coli 16S rRNA, based on comparative sequence analysis in which the folding pattern is assumed to be conserved across different species. The molecule can be subdivided into four domains—I, II, III, and IV—on the basis of contiguous stretches of the chain that are closed by long-range base-pairing interactions. I, the 5 -domain, includes nucleotides 27 through 556. II, the central domain, runs from nucleotide 564 to 912. Two domains comprise the 3 -end of the molecule. Ill, the major one, comprises nucleotides 923 to 1391. IV, the 3 -terminal domain, covers residues 1392 to 1541. 

If a phylogenetic comparison is made of the 16S-Iike rRNAs from an archae-bacterium Halobacterium volcanii), a eubacterium E. coli), and a eukaryote (the yeast Saccharomyces cerevisiae), a striking similarity in secondary structure emerges (Figure 12.40). Remarkably, these secondary structures are similar despite the fact that the nucleotide sequences of these rRNAs themselves exhibit a low degree of similarity. Apparently, evolution is acting at the level of rRNA secondary structure, not rRNA nucleotide sequence. Similar conserved folding patterns are seen for the 23S-Iike and 5S-Iike rRNAs that reside in the... 

No sequence homologies can be detected. This is, perhaps, not surprising. The X-ray structure analysis of lysozyme by Phillips has shown that the polypeptide chain is folded in a way which puts none of the amino acids in sequential vicinity of the catalytic Asp-52 and Glu-37 that are near to the bound substrate. Comparable folding patterns can probably be realized with widely differing arrangements of amino acids, and thus the apparent lack of homologies. 

This pardaxin model is not unique. We have developed several similar models that are equally good energetically and equally consistent with present experimental results. It is difficult to select among these models because the helices can be packed a number of ways and the C-terminus appears very flexible. Our energy calculations are far from definitive because they do not include lipid, water, ions, membrane voltage, or entropy and because every conformational possibility has not been explored. The model presented here is intended to illustrate the general folding pattern of a family of pardaxin models in which the monomers are antiparallel and to demonstrate that these models are feasible. 

The crystal structure of the HNL isolated from S. bicolor (SbHNL) was determined in a complex with the inhibitor benzoic acid." The folding pattern of SbHNL is similar to that of wheat serine carboxypeptidase (CP-WII)" and alcohol dehydrogenase." A unique two-amino acid deletion in SbHNL, however, is forcing the putative active site residues away from the hydrolase binding site toward a small hydrophobic cleft, thereby defining a completely different active site architecture where the triad of a carboxypeptidase is missing. 

A. Protein Spectral Qualitative and Quantitative Techniques 1. Qualitative Fold Patterns... 

Figure 5.2 Schematic representation of the folding pattern for the N-lobe (left) and C-lobe (right) of human lactoferrin. From Anderson et al., 1989. Reproduced by permission of Academic Press.

Threading essentially entails comparing the sequence of the polypeptide whose three-dimensional structure you wish to predict with the database sequences known to generate specific fold patterns. Computer programs can then be used to estimate the probability of the target sequence adopting each known folding structure. 

Fig. 7. Ribbon Ca model of H4 showing the folding pattern of an exemplar histone. The canonical histone fold includes one long medial a-helix (mH) with two shorter a-helices towards the N- and C-termini (NH, CH), bound by loops (NL, CL) to the primary helix.

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