Super-secondary structure, protein

Anderson, W.F., et al. Proposed a-helical super-secondary structure associated with protein-DNA recognition. 

Sauer, R.T., et al. Homology among DNA-binding proteins suggests use of a conserved super-secondary structure. Nature 298 447-451, 1982. 

Figure 4.8 Super-secondary structures found in proteins (a) P-a-P motifs (b) anti-parallel P-sheets connected by hairpin loops (c) a-a motifs. (From Voet and Voet, 2004. Reproduced with permission from John Wiley Sons., Inc.)...

The association of secondary structures to give super-secondary structures, which frequently constitute compactly folded domains in globular proteins, is completed by the a-a motifs in which two a-helices are packed in an anti-parallel fashion, with a short connecting loop (Figure 4.8c). Examples of these three structural domains, often referred to as folds, are illustrated in Figures 4.9—4.11. The schematic representation of the main chains of proteins, introduced by Jane Richardson, is used with the polypeptide backbone... 

There has been considerable effort on the prediction of secondary and tertiary structures of protein from the amino acid sequence using computeraided minimal potential energy calculations8). The question as to how a primary amino acid sequence begins to produce secondary and super-secondary structures and fold into its equilibrium tertiary structure and functional domains is a very active field of structural biochemistry. A related problem is the mechanism by which a protein unfolds or denatures 20) which is of fundamental interest in the protein adsorption process. 

Nagano, K. Logical analysis of the mechanism of protein folding IV. Super secondary structures. J. Molec. Biol. 109, 235-250 (1977). 

The tertiary structure of proteins, also called the super-secondary structure, denotes the way in which the secondary structures are assembled in the biologically active molecule, (Figure 7.27b). These are described in terms of motifs3, that consist of a small number of secondary structure elements linked by turns, such as (oc-helix - turn -a-helix). Motifs are further arranged into larger arrangements called folds, which can be, for example, a collection of / -sheets arranged in a... 

Coiled coil, motifs of super-secondary structure found in proteins. Approximately 2-3% of aU proteins form coiled coils, where two to seven amphipathic a-helices are wrapped around each other, like the strands of a rope. The interaction surface of these amphipathic helices is of hydrophobic nature, and leucine is often found in the position of the hydrophobic amino acids (leucine zipper). This hydrophobic interaction provides, in an aqueous environment, the driving force for the di- or oligomerization. Coiled coils of two or three helical domains are the most commonly found types. In the former case, the two helices are wound up against each other in a left-handed twist with a seven-residue periodicity. Packing of unpolar side chains (u) into a hydrophobic core mainly contributes to the stability of this super-secondary fold. The dimeric coiled coU is, for example, responsible for DNA recognition by some transcription factors. 

Taylor, W. and Thorton, J. Recognition of super-secondary structure in proteins. J. Mol. Biol. 173 487-514, 1984. 

Macroconformations consisting of two or three helices intertwined with each other are also sometimes called super helices or super secondary structures. An example is deoxyribonucleic acid, which forms a double helix from two complementary chains, each in the form of a helix (see Section 29). With synthetic polymers, both it-poly(methyl methacrylate) and poly(/ -hydroxybenzoic acid) appear to form double helices. Triple helices are, for example, formed by the protein, collagen (see Section 30). 

Super-secondary Structure.—As can be seen from Table 1 the majority of globular protein structures can be described in terms of varying amounts of close packed a-helical or yS-sheet secondary structure. Similarities in the packing pattern of these... 

The basic thesis has served as the stimulus for a large number of studies directed towards the prediction of protein three-dimensional structures from their amino-acid sequences alone. Implicit in most of the predictive methods investigated are two concepts (i) that there is in the protein the clearly-observed hierarchical structural arrangement (primary structure - secondary structure - secondary aggregates or super-secondary structure - domains - total structure) which has already been discussed in the previous section and (ii) that the folding process of a random chain to give the stable native structure is kinetically-controlled and that it proceeds via a characteristic and predictable pathway. This pathway is visualized as requiring nucleation at various sites around which the subsequent... 

Various schemes have been developed for the classification of protein three-dimensional structures. One common scheme is the classification based on the four tertiary super classes, namely, all a (proteins having mainly a-helix secondary structure), all P (mainly P-sheet secondary structure), a+p (segment of a-helices followed by segment of P-sheets), and o/p (alternating or mixed a-helix and P-sheet segments) (Levitt, 1976). A fifth class is often added to account for globular proteins with irregular secondary... 

The basic information of protein tertiary structural class can help improve the accuracy of secondary structure prediction (Kneller et al., 1990). Chandonia and Karplus (1995) showed that information obtained from a secondary structure prediction algorithm can be used to improve the accuracy for structural class prediction. The input layer had 26 units coded for the amino acid composition of the protein (20 units), the sequence length (1 unit), and characteristics of the protein (5 units) predicted by a separate secondary structure neural network. The secondary structure characteristics include the predicted percent helix and sheet, the percentage of strong helix and sheet predictions, and the predicted number of alterations between helix and sheet. The output layer had four units, one for each of the tertiary super classes (all-a, all-p, a/p, and other). The inclusion of the single-sequence secondary structure predictions improved the class prediction for non-homologous proteins significantly by more than 11%, from a predictive accuracy of 62.3% to 73.9%. 

The protein folding problem - the ability to predict a protein fold from its sequence - is one of the major prizes in computational chemistry. Molecular dynamics simulations of solvated proteins is currently not a feasible approach to this problem. However, Duan and Kollman have shown that a 1 ps simulation on a small hydrated protein, here the 36 residue villin headpiece, is now possible using a massively parallel super computer.33 The native protein is estimated to fold in about 10-100 ps and so the simulation can only be used to study the early stages of protein folding. Nevertheless, starting from an extended structure the authors were able to observe hydrophobic collapse and secondary structure formation (helix 2 was well formed, helices 1 and 3 were partially formed and the loop connecting helices 1 and 2 was also partially... 

The right-handed helices, which seem to be the preferred secondary structure, have 3.6 amino acids per tnm and are stabilised by hydrogen bonding between the NH and the CO groups further along the chain. Helices of this kind are associated in different ways to form tertiary structures of super helices in other fibrous proteins such as collagen, elastin, wool and so forth (Figure 10.16). 

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