Helix and 3-Sheet

Why should the cores of most globular and membrane proteins consist almost entirely of a-helices and /3-sheets The reason is that the highly polar N—H and C=0 moieties of the peptide backbone must be neutralized in the hydrophobic core of the protein. The extensively H-bonded nature of a-helices and /3-sheets is ideal for this purpose, and these structures effectively stabilize the polar groups of the peptide backbone in the protein core. 

Implicit in the presumption of folding pathways is the existence of intermediate, partially folded conformational states. The notion of intermediate states on the pathway to a tertiary structure raises the possibility that segments of a protein might independently adopt local and well-defined secondary structures (a-helices and /3-sheets). The tendency of a peptide segment to prefer a particular secondary structure depends in turn on its amino acid composition and sequence. 

Repeating 3D units such as a-helices and (3-sheets (buried main chain H bonds)... 

Figure 11.37 Notional depiction of dendron packing in a-helical and /3-sheet structural forms. Reprinted from Shao et al. (2007). Copyright 2007 American Chemical Society.

As the last example of a helix-sheet transition, Pagel et al. (2006) demonstrate a coiled coil peptide adopting three types of secondary structures and the transition between random coil, a-helical, and /3-sheet hbers can be simply triggered by changing the pH or peptide concentration. 

The current model for Mg + transport is illustrated in Figure 8 and is believed to be controlled by a magnesium sensor consisting of two specific Mg + binding sites located on the outside of the funnel in the a a sandwich domain that spans the wiUow helices and /3-sheets ° . Studies of similar binding sites in other proteins indicates that these sites will probably have an affinity for Mg + that is slightly less than the average free concentration of Mg + in cells . When the concentration of Mg in the cell drops below... 

Where they occur together in proteins, a helices and /3 sheets generally are found in different structural layers. This is because the backbone of a polypeptide segment in the /3 conformation (Fig. 4-7) cannot readily hydrogen-bond to an a helix aligned with it. 

Some common structural motifs combining a-helices and 3-sheets. The names describe their schematic appearance. [Note The Greek key takes its name from a design often found in classical Greek pottery.]... 

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. 

The most stable elements of secondary structure of peptides and proteins are turns, helices, and extended conformations. Within each of these 3D-structures the most commonly found representatives are (3-turns,a-helices, and antiparallel (3-sheet conformations, respectively. y-TurnsJ5 310-helices, poly(Pro) helices, and (3-sheet conformations with a parallel strand arrangement have also been observed, although less frequently. Among the many types of (3-turns classified, type-I, type-II, and type-VI are the most usual, all being stabilized by an intramolecular i <— i+3 (backbone)C=0 -H—N(backbone) H-bond and characterized by either a tram (type-I and type-II) or a cis (type-VI) conformation about the internal peptide bond. In the type-I (3-turn a helical i+1 residue and a quasi-helical 1+2 residue are found, whereas in the type-II (3-turn the i+1 residue is semi-extended and the 1+2 residue is also quasi-helical but left-handed. This latter corner position may be easily occupied by the achiral Gly or a D-amino acid residue. 

Antithrombin is a member of the SERPIN superfamily of proteins, which includes the inhibitors a2 an1 Pbsniin, ar antichymotrypsin, and a -proteinase inhibitor (79). Antithrombin is considered to be the primary inhibitor of coagulation (80) and targets most coagulation proteases as well as the enzymes trypsin, plasmin, and kallikrein (81). Inhibition takes place when a stoichiometric complex between the active site serine of the protease and the ARG393-SER394 bond of antithrombin forms (82,83), The tertiary structure of antithrombin resembles a,-antitrypsin in that it is folded into N-terminal domain helices and (3-sheets. This tertiary structure is maintained by the formation of three disulfide bonds (71). Four glycosylation sites exist on human... 

The goal of protein-structure prediction is to derive the tertiary structure of the protein (defined as the manner in which the protein is bent or folded in three dimensions) given the sequence of amino acids (referred to as the primary structure). In between the primary and tertiary structure is the secondary structure which consists of regularly recurring arrangements of the protein chain in one-dimension (i e, a-helices and (3-sheets)... 

This nomenclature may also describe the sequence of events in the folding process the primary sequence adopts secondary structural elements which then fold into the correct tertiary structure. Pauling first postulated that the hydrogen bond played a large role in the folding process The importance of the hydrogen bond in stabilizing the secondary-structural elements, a-helices and (3-sheets, was quite clear from his earlier work [3-5],... 

There are similarities in the helices and /3 sheets between baboon a-lactalbumin and hen egg-white lysozyme, as summarized in Table V. However, there are important differences, for example, in hen egg-white lysozyme residues 41—60 form an irregular antiparallel j8-pleated sheet in this protein a residue is deleted at position 48 (human lysozyme numbering), but two residues are deleted in a-lactalbumin at positions 47 and 48 (human lysozyme numbering). Residue 47 is the most exposed to solvent in the hen egg-white lysozyme and forms part of the irregular 0 turn. These residues occur in a -pleated sheet and the deletions are accommodated with minimal disruption to the pleated sheet (see the comparison in Acharya et al., 1989). 

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