Secondary protein structure supersecondary

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. 

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. 

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. 

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. 

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. 

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.)... 

The association of secondary structures can give rise to so-caUed supersecondary structures, often referred to as folds, which frequently constitute compactly folded domains in globular proteins. They are presented in Figure 3.12... 

Certain combinations of secondary structure are present in many proteins and frequently exhibit similar functions. These combinations are called motifs or supersecondary structure. For example, an a helix separated from another a helix by a turn, called a helix-turn-helix unit, is found in many proteins that bind DNA (Figure 2.51). 

Many globular proteins contain combinations of a-helix and /Tpleated sheet secondary structures (Figure 5.20). These patterns are called supersecondary structures. In the /la/1 unit, two parallel /Tpleated sheets are connected by an a-helix segment. In the fi-meander pattern, two antiparallel /1-sheets are connected by polar amino acids and glycines to effect an abrupt change in direction of the polypeptide chain called reverse or fi-turns. In aa-units, two successive a-helices separated by a loop or nonhelical segment become enmeshed because of compatible side chains. Several j8-barrel arrangements are formed when various... 

Protein folding in cells probably involves multiple pathways. Initially, regions of secondary structure may form, followed by folding into supersecondary structures. Large ensembles of folding intermediates are rapidly brought to a single native conformation. 

There is a natural hierarchy in proteins (see Figure 15.1) which allows the complex three-dimensional structure to be simplified and categorized as combinations of smaller motifs. At the atom level there are patterns of side-chain interactions at the backbone level we see formation of secondary structure (a helix, P sheet and yS turn) and loop families these combine to give supersecondary structures (e.g. P hairpins) and motifs (e.g. Greek key) and ultimately the whole tertiary and quaternary structure. In this chapter we present an overview of current patterns which are observed... 

FIGURE 4.9 Motifs and modules. Motifs are repeated supersecondary structures, sometimes called modules. All of these have a particular secondary structure that is repeated in the protein. (Reprinted from Protein Modules, "Trends in Biochemical Sciences, Vol. 16, pp. 13—17, Copyright 1991, xvith permission from Elsevier.)... 

The most common secondary structures are the a-helix and /3-sheet. Native proteins may have combinations of various secondary structures Regions of secondary structures can be combined to form supersecondary structures, motifs, and domains. 

---