Protein structure antiparallel

Beta strands can also combine into mixed P sheets with some P strand pairs parallel and some antiparallel. There is a strong bias against mixed P sheets only about 20% of the strands inside the p sheets of known protein structures have parallel bonding on one side and antiparallel bonding on the other. Figure 2.7 illustrates how the hydrogen bonds between the p strands are arranged in a mixed P sheet. 

As they occur in known protein structures, almost all P sheets—parallel, antiparallel, and mixed—have twisted strands. This twist always has the same handedness as that shown in Figure 2.7, which is defined as a right-handed twist. 

On the basis of simple considerations of connected motifs, Michael Leviff and Cyrus Chothia of the MRC Laboratory of Molecular Biology derived a taxonomy of protein structures and have classified domain structures into three main groups a domains, p domains, and a/p domains. In ct structures the core is built up exclusively from a helices (see Figure 2.9) in p structures the core comprises antiparallel p sheets and are usually two P sheets packed... 

Figure 5.10 Idealized diagrams of the Greek key motif. This motif is formed when one of the connections of four antiparallel fi strands is not a hairpin connection. The motif occurs when strand number n is connected to strand + 3 (a) or - 3 (b) instead of -r 1 or - 1 in an eight-stranded antiparallel P sheet or barrel. The two different possible connections give two different hands of the Greek key motif. In all protein structures known so far only the hand shown in (a) has been observed.

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. 

Due to the ready accessibility of SH2 domains by molecular biology techniques, numerous experimentally determined 3D structures of SH2 domains derived by X-ray crystallography as well as heteronuclear multidimensional NMR spectroscopy are known today. The current version of the protein structure database, accessible to the scientific community by, e.g., the Internet (http //www.rcsb.org/pdb/) contains around 80 entries of SH2 domain structures and complexes thereof. Today, the SH2 domain structures of Hck [62], Src [63-66], Abl [67], Grb2 [68-71], Syp [72], PLCy [73], Fyn [74], SAP [75], Lck [76,77], the C- and N-terminal SH2 domain ofp85a [78-80], and of the tandem SH2 domains Syk [81,82], ZAP70 [83,84], and SHP-2 [85] are determined. All SH2 domains display a conserved 3D structure as can be expected from multiple sequence alignments (Fig. 4). The common structural fold consists of a central three-stranded antiparallel ft sheet that is occasionally extended by one to three additional short strands (Fig. 5). This central ft sheet forms the spine of the domain which is flanked on both sides by regular a helices [49, 50,60]. 

There is a correlation between the backbone conformations which commonly flank disulfides and the frequency with which disulfides occur in the different types of overall protein structure (see Section III,A for explanation of structure types), although it is unclear which preference is the cause and which the effect. There are very few disulfides in the antiparallel helical bundle proteins and none in proteins based on pure parallel /3 sheet (except for active-site disulfides such as in glutathione reductase). Antiparallel /3 sheet, mixed /8 sheet, and the miscellaneous a proteins have a half-cystine content of 0-5%. Small proteins with low secondary-structure content often have up to 15-20% half-cystine. Figure 52 shows the structure of insulin, one of the small proteins in which disulfides appear to play a major role in the organization and stability of the overall structure. 

In a very broad overview of the structural categories one can state several statistical correlations with type of function. Hemes are almost always bound by helices, but never in parallel a//3 structures. Relatively complex enzymatic functions, especially those involving allosteric control, are occasionally antiparallel /3 but most often parallel a//3. Binding and receptor proteins are most often antiparallel /3, while the proteins that bind in those receptor sites (i.e., hormones, toxins, and enzyme inhibitors) are most apt to be small disulfide-rich structures. However, there are exceptions to all of the above generalizations (such as cytochrome cs as a nonhelical heme protein or citrate synthase as a helical enzyme), and when one focuses on the really significant level of detail within the active site then the correlation with overall tertiary structure disappears altogether. For almost all of the dozen identifiable groups of functionally similar proteins that are represented by at least two known protein structures, there are at least... 

McGhee JD, Felsenfeld G (1980) Nucleosome structure. Annu Rev Biochem 49 1115-1156 Melby TE, Ciampagho CN, Briscoe G, Erickson HP (1998) The symmetrical structure of structural maintenance of chromosomes (SMC) and MukB proteins long, antiparallel coiled coils, folded at a flexible hinge. J Cell Biol 142 1595-1604... 

The duplex is a right-handed double helix with 10 bases per turn. The diameter of the helix is 20 A (2 nm) and the pitch is 34 A (3.4 nm). The sugar-phosphate backbone is on the outside of the helix, and the two antiparallel chains are connected by the hydrogen-bonded bases. The DNA in prokaryotes and eukaryotes is generally found in the duplex form, although there are some single-stranded DNA viruses. DNA is a very robust molecule in comparison with many proteins. The simple double-helical secondary structure is readily reassembled after denaturation, unlike the complex tertiary protein structures that can denature... 

The frequency of the amide I peak observed in the lens is sensitive to protein secondary structure. From its absolute position at 1672 cm-1, which is indicative for an antiparallel pleated 3-sheet structure, and the absence of lines in the 1630-1654 cm-1 region, which would be indicative of parallel (1-sheet and a-helix structures, the authors could conclude that the lens proteins are all organized in an antiparallel, pleated 3-sheet structure [3]. Schachar and Solin [4] reached the same conclusion for the protein structure by measuring the amide I band depolarization ratios of lens crystallins in excised bovine lenses. Later, the Raman-deduced protein structure findings of these two groups were confirmed by x-ray crystallography. 

Open-face sandwich In protein structures this term describes a single antiparallel l3 sheet that has a layer of a helices and loops on one side only. 

The crystal structure of the active site of PARP has been described (5).It is made up of a five-stranded antiparallel beta sheet and a four-stranded mixed beta sheet (Fig. 11.2). The two beta sheets are connected by two hydrogen bonds. The beta sheet structure is supported by a surrounding protein structure made up of five alpha helices, three 3iq helices, and beta sheet excursions. The active site is... 

The cooperative effects in secondary protein structures, helix and sheet have been reported [53]. The linear chain of formamide which resembles peptides has large cooperativity in H-bond, which is 2.5 times that of formamide dimer. For the parallel and antiparallel sheet in secondary protein structures, there was no cooperativity in the parallel direction, while significant cooperativity exists in perpendicular direction. In methanol solvent system, the cooperative effects were reduced, indicating that the cooperativity is due to the polarization effect. 

Figure 1. Schematic representations of protein structures (a) myohemerythrin, an a-helical protein with antiparallel helices ( >) V2 domain of an immunoglobulin, a (3-sheet protein (c) triose phosphate isomerase, a parallel a-ff protein with a central (3 barrel (d) carboxypepti-dase, a parallel a- 3 protein with a central ( -sheet structure (e)para-hydroxybenzoate hydrolase, a complex protein structure with more than one domain. (From Ref. S3 courtesy of J. Richardson.)...

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]. 

Most approaches to the interpretation of protein structure based on circular dichroism spectra assume that the conformational contributions from a-helix, parallel ( ) and antiparallel (a ) (3-sheet, (3-bend, and irregular regions are additive such that... 

Fig. 7.17. Structure of the Vl and Cl domains of IgG. Layers of antiparallel 3-sheets are stacked in these domains, which have been referred to as collapsed -barrels. The antigen binds between the Vh and Vl immunoglobulin folds, and NOT in the barrel. The Cl domain is also called the immunoglobulin fold. (Top modified from Richardson JS. Adv Protein Chem. The anatomy and taxonomy of protein structure 1981 34 167 bottom reprinted in part with permission from Edmundson AB, et al. Biochemistry 1975 14 3954. 1975 American Chemical Society.)...

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