Antiparallel P-structure

The p sheets have the usual twist, and when two such twisted p sheets are packed together, they form a barrel-like structure (Figure 5.1). Antiparallel P structures, therefore, in general have a core of hydrophobic side chains inside the barrel provided by residues in the P strands. The surface is formed by residues from the loop regions and from the strands. The aim of this chapter is to examine a number of antiparallel p structures and demonstrate how these rather complex structures can be separated into smaller comprehensible motifs. 

In the first edition of this book this chapter was entitled "Antiparallel Beta Structures" but we have had to change this because an entirely unexpected structure, the p helix, was discovered in 1993. The p helix, which is not related to the numerous antiparallel p structures discussed so far, was first seen in the bacterial enzyme pectate lyase, the stmcture of which was determined by the group of Frances Jurnak at the University of California, Riverside. Subsequently several other protein structures have been found to contain p helices, including extracellular bacterial proteinases and the bacteriophage P22 tailspike protein. 

The number of possible ways to form antiparallel p structures is very large. The number of topologies actually observed is small, and most p structures fall into these three major groups of barrel structures. The last two groups—the Greek key and jelly roll barrels—include proteins of quite diverse function, where functional variability is achieved by differences in the loop regions that connect the p strands that build up the common core region. 

Most of the known antiparallel p structures, including the immunoglobulins and a number of different enzymes, have barrels that comprise at least one Greek key motif. An example is 7 crystallin, which has two consecutive Greek key motifs in each of two barrel domains. These four motifs are homologous in terms of both their three-dimensional structure and amino acid sequence and are thus evolutionarily related. 

In addition to the antiparallel p-structures, there is a novel fold called the P helix. In the p-helix structures the polypeptide chain is folded into a wide helix with two or three p strands for each turn. The p strands align to form either two or three parallel p sheets with a core between the sheets completely filled with side chains. 

Shape and dimension, (a) Tropomyosin, a 70-kd muscle protein, is a two-stranded a-helical coiled coil. Estimate the length of the molecule, (h) Suppose that a 40-residue segment of a protein folds into a two-stranded antiparallel P structure with a 4-residue hairpin turn. What is the longest dimension of this motif ... 

The tendency for a P sheet to fold into a cylinder is encouraged in antiparallel P structures by the existence of a common irregularity called the p bulge. Tizs As illustrated in Fig. 2-18, a p bulge contains an extra residue inserted into one of the chains. In the second... 

Several inhibitor-protease complexes have been crystallized and details of their interactions are known. For example, the pancreatic trypsin inhibitor binds at the active site of trypsin with Kf >10 M at neutral pH. The two molecules fit snugly together, °497 inhibitor being bound as if if were a peptide substrate with one edge of the inhibitor molecule forming an antiparallel P structure with a peptide chain in the enzyme. Lysine 15, which forms part of this P structure, enters the specific Pj binding sife for a basic amino acid in a substrate. Thus, the protease inhibitor is a modified substrate which may actually undergo attack at the active site. However, the fit between the two... 

NAD+-pyruvate is shown in Fig. 8. The enzyme has an extensive amount of secondary structure. Ramachandran diagrams are shown in Fig. 9. Estimates of the proportion of amino acid residues located in the helices depend on the precise definition of secondary structure and vary around 40%. Three different p structures are found in LDH and account for around 23% of all residues. The amino terminal half of the molecule contains a six-stranded parallel sheet whereas the carboxy terminal half of the subunit has two three-stranded antiparallel p structures. The parallel sheet which is mainly in the interior of the molecule, exposes two edges to the solvent and one to a subunit interface. Thus, most of the residues in this structure are hydrophobic. The high concentration of / -branched residues such as valine, isoleucine, and threonine as well as the twist present in all observed p structures 143) can be seen in Fig. 

The two small antiparallel p structures are fairly irregular but do have the same twist as the parallel sheet. Each p structure consists of two long and one short strand coiled around an imaginary axis to form a helix where the sense is left-handed on following the path of the polypeptide chain. 

Ramachandran plot for alanylalanine showing the fully allowed regions (double-hashed) and partially allowed regions (single-hatched) of ( ) and / angles (see Fig. 4-6). The coordinates for the parallel and antiparallel p structures (Pp and Pa, respectively) and for the left-handed and right-handed a helices (aL and ttR, respectively) are indicated. 

Antiparallel p structures usually have one side buried and one side exposed, so there is a hydrophobic-hydrophilic periodicity with a repeat of about two residues for each strand. 

The p class contains the parallel and antiparallel p structures. The p strands are usually arranged in two p sheets that pack against each other and form a distorted barrel structure. Three major types of p barrels exist, the up-and-down barrels, the Greek key barrels,and the jelly roll barrels (see Figure 6). Most known antiparallel p structures, including the... 

Figure 8 illustrates the solid-state IR spectra some interesting POE-bound [L-Lys-(Z)] homooligomers. Short chains with n = 1-3 predcminantly exist in a disordered conformation, oligomers with n = 4-12 adopt an antiparallel P-structure,... 

Systematic investigations give evidence that homooligopeptides consisting of amino acids with linear side chains tend to adopt the antiparallel P-structure. Homooligomers with P-branched and aromatic residues, e.g. [L-Phe] and [L-Tyr(Bzl)] predominantly prefer the parallel P-sheet type [L-Leu] with y-branched amino acids was shown to adopt both of these structural variants... 

It is conventional in peptide synthesis to start out in a solvent of low polarity (e.g. CH2CI2) and to add solvents of higher polarity such as DMF and DMSO as soon as the solubility of the growing pq)tide chain falls off. The addition of DMSO or DMF causes a disruption of the P-sheet structure as monitored by the lowered intensity of the amide-I IR band at 1630 cm (Fig. 13) because this band is indicative of the presence of an antiparallel p-structure. 

A distinct type of polymorphism was observed in the AP(l-40)-Iowa mutant D23N [44, 118]. In the same fibril preparation both parallel and antiparallel P-structures coexisted, the latter representing the major conformation. This finding illustrates that a single disease-related mutation can have extensive consequences for amyloid structure. 

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