Supersecondary structures proteins

Simple combinations of a few secondary strucfure elements with a specific geometric arrangement have been found to occur frequently in protein structures. These units have been called either supersecondary structures or motifs. We will use the term "motif" throughout this book. Some of these motifs can be associated with a particular function such as DNA binding others have no specific biological function alone but are part of larger strucfural and functional assemblies. 

Investigations of static structures include architectural descriptions, comparisons and classifications, and identifications of recurrent patterns such as supersecondary structures. Examples include the classification of types of proteins by Levitt and Chothia (28), the hierarchical analysis of protein structures by Rose (29), or the comparison of globin structures by Lesk and Chothia (30). 

High resolution X-ray analysis of protein structures shows that the conformational categories of the connecting peptides which link the a-helices and -sheets are limited. Such well defined types of folding units, such as aa- and PP-hairpins, and aP- and Pa-arches, are referred to as supersecondary structures. One important step towards building a tertiary structure from secondary structures is to identify these supersecondary structure... 

Supersecondary structure A pattern of protein structure that is not an entire domain but is at a higher level than secondary structure. Examples are yS barrels and Greek-key structures. 

The simplest supersecondary 8-structural motif is formed by two sequential P strands. These can be in the same sheet, in which case they can either be antiparallel or parallel to one another (Figure 15.13a and 15.13b), or they can be in different sheets, forming an inter-sheet connection (Figure 15.13c). The pie chart in Figure 15.14 shows the fraction of sequential strand connections that are parallel, antiparallel and inter-sheet. The data were extracted automatically from a non-homologous data set of 90 protein structures in the Brookhaven Data Bank [7]. 

An interesting hierarchical Monte Carlo procedure for the prediction of protein structures has been proposed recently by Rose et al. [209]. Their model employs an all-atom representation of the main chain and a crude representation of the side groups interacting via a simple contact potential. The method seems to be quite accurate in the prediction of protein secondary and supersecondary structure however, the overall global accuracy of the folded structures is rather low. 

Many proteins share structural similarities due to the evolutionary process involving substitutions, insertions and deletions in amino add sequences. Consequently protein structures can be characterized according to their connnon substructures (supersecondary structures, e.g. motifs, domains). For proteins with conserved functions, the structural environments of critical active site residues are also conserved. In an attempt to better understand seqnence-structuie relationships and the underlying evolutionary processes that give rise to different fold famihes, a variety of structure classification schemes have been established. Analyses of the 3D structures archived in PDB generate various databases for the specification/search of characteristic substructures and protein structure classifications (Table 16.6). 

The above-mentioned incremental nature of protein stability has been established by detailed studies on model proteins such as phage T4 lysozyme, and by rational protein design. As mentioned, stabilization may involve all levels of the hierarchy of protein structure, local packing of the polypeptide chain, secondary and supersecondary structural elements, domains, and subunits. Approaches to assign specific structural alterations to changes in stability are summarized in Table I. 

A description of the protein-structure hierarchy is incomplete without a discussion of structural motifs, which are critical to an understanding of protein structure [17]. Identification of recurring motifs in protein structures has refined our knowledge of the protein-structure hierarchy these motifs occur at all levels from primary to tertiary. The Phe-Asp-Thr-Gly-Ser sequence found in the active site of all aspartic acid proteinases, and the Gly-Gly-X-Leu sequence (where X represents any amino acid residue) that predicts a 3-strand for the last two residues [17], are examples of sequence motifs a-helices, P-strands, and turns are examples of secondary-structural motifs PaP and PxP units, P-hairpins, and Greek keys are examples of supersecondary-structural motifs and four-a-helix bundles and TIM barrels are examples of tertiary-structural motifs. The tertiary fold of a protein is characterized by its tertiary-structural motif. 

F. 2.9. Main structural motifs in globular proteins. (A) ordered structures (1) a-helix from Cozey and Pauling (1956) (2) segment of extended structure, parallel and anti parallel P sheets from Corey and Pauling (1956) (3) P turns type I and II from Lewis et al. (1971). (B) Supersecondary structures. (C) Diagrammatic protein structures left, chymotrypsin with two P barrels right, triose phosphate isomerase (altemance of helices and P barrels) (from Schulz and Schirmer, 1979) (courtesy of Schulz). 

Perhaps one of the most promising aspects is the prediction of supersecondary structures in proteins which will allow one to reach a new level of prediction in protein structure. A further step would be to determine the rules for the formation and then the association of domains in a protein. 

Y Cm, RS Chen, WEI Wong. Protein folding simulation with genetic algorithm and supersecondary structure constraints. Proteins 31 247-257, 1998. 

Godzik, A., and Skolnick, J. (1992). Sequence-structure matching in globular proteins application to supersecondary and tertiary structure determination. Proc. Natl. Acad. Sci. U.S.A. 89, 12098-12102. 

The complex structures of globular proteins can be analyzed by examining stable substructures called supersecondary structures,... 

Globular proteins are constructed by combining secondary structural elements (a-helices, 3-sheets, nonrepetitive sequences). These form primarily the core region—that is, the interior of the molecule. They are connected by loop regions (for example, 3-bends) at the surface of the protein. Supersecondary structures are usually pro duced by packing side chains from adjacent secondary structural elements close to each other. Thus, for example, a-helices and 3-sheets that are adjacent in the amino acid sequence are also usu ally (but not always) adjacent in the final, folded protein. Some of the more common motifs are illustrated in Figure 2.8. 

Superoxide dismutase 166 Supersecondary structure 9, 20 Surface charge of protein 179-180,... 

Miles, M.J., Carr, H.J., McMaster, T.J., I Anson, K.J., Belton, P.S., Morris, V., Field, J.M., Shewry, P.R., Tatham, A.S. 1991. Scanning tunneling microscopy of a wheat seed storage protein reveals details of an unusual supersecondary structure. Proc Natl Acad Sci USA 88 68-71. 

Fig. 4-11 Diagrammatic representation of the supersecondary fi-a-fi folding unit of a protein, p regions are represented by the arrows, while the a-helical segment is indicated by the coiled structure. Approximate positions of hydrogen bonds are shown with dashed lines.

In the complete structure, secondary-structured regions are assembled into compact units. The interactions between secondary structural units seem to be stereochemically specific. This is called the tertiary structure of the protein. (Certain common patterns of interaction between secondary structural units are known as supersecondary structures.)... 

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