Proteins regular structure

A model of a Pn helix formed by alanine side chains is illustrated for reference in Figure 13B (see color insert), while Figure 13A illustrates the common occurrence of the Pn backbone conformation among residues outside regions of regular secondary structure (Kleywegt and Jones, 1996 Serrano, 1995 Stapley and Creamer, 1999) in protein structures from the Protein Data Bank. 

The unit cell considered here is a primitive (P) unit cell that is, each unit cell has one lattice point. Nonprimitive cells contain two or more lattice points per unit cell. If the unit cell is centered in the (010) planes, this cell becomes a B unit cell for the (100) planes, an A cell for the (001) planes a C cell. Body-centered unit cells are designated I, and face-centered cells are called F. Regular packing of molecules into a crystal lattice often leads to symmetry relationships between the molecules. Common symmetry operations are two- or three-fold screw (rotation) axes, mirror planes, inversion centers (centers of symmetry), and rotation followed by inversion. There are 230 different ways to combine allowed symmetry operations in a crystal leading to 230 space groups.12 Not all of these are allowed for protein crystals because of amino acid asymmetry (only L-amino acids are found in proteins). Only those space groups without symmetry (triclinic) or with rotation or screw axes are allowed. However, mirror lines and inversion centers may occur in protein structures along an axis. 

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]. 

Figure 11.3 The effect of imino acids on protein structure. The presence of the imino acids proline and hydroxyproline introduces a constraint into the angles of the peptide bond which results in a bend in the previously regular chain structure.

The a-helix is the classic element of protein structure. A single a-helix can order as many as 35 residues whereas the longest strands include only about 15 residues, and one helix can have more influence on the stability and organization of a protein than any other individual structure element. a-Helices have had an immense influence on our understanding of protein structure because their regularity makes them the only feature readily amenable to theoretical analysis. 

Successful examples of the sort of correlations postulated above would add additional independent pieces of information for use in a combined strategy of noncrystallographic protein structure determination. Empirical regularities such as the handedness of crossover... 

From the physics point of view, the system that we deal with here—a semiflexible polyelectrolyte that is packaged by protein complexes regularly spaced along its contour—is of a complexity that still allows the application of analytical and numerical models. For quantitative prediction of chromatin properties from such models, certain physical parameters must be known such as the dimensions of the nucleosomes and DNA, their surface charge, interactions, and mechanical flexibility. Current structural research on chromatin, oligonucleosomes, and DNA has brought us into a position where many such elementary physical parameters are known. Thus, our understanding of the components of the chromatin fiber is now at a level where predictions of physical properties of the fiber are possible and can be experimentally tested. 

Perhaps the more remarkable features of [myoglobin] are its complexity and its lack of symmetry. The arrangement seems to be almost totally lacking in the kind of regularities which one instinctively anticipates, and it is more complicated than has been predicted by any theory of protein structure. 

The term secondary structure refers to the local conformation of some part of a polypeptide. The discussion of secondary structure most usefully focuses on common regular folding patterns of the polypeptide backbone. A few types of secondary structure are particularly stable and occur widely in proteins. The most prominent are the a helix and /3 conformations described below. Using fundamental chemical principles and a few experimental observations, Pauling and Corey predicted the existence of these secondary structures in 1951, several years before the first complete protein structure was elucidated. 

As in the case of protein structure (Chapter 4), it is sometimes useful to describe nucleic acid structure in terms of hierarchical levels of complexity (primary, secondary, tertiary). The primary structure of a nucleic acid is its covalent structure and nucleotide sequence. Any regular, stable structure taken up by some or all of the nucleotides in a nucleic acid can be referred to as secondary structure. All structures considered in the remainder of this chapter fall under the heading of secondary structure. The complex folding of large chromosomes within eukaryotic chromatin and bacterial nucleoids is generally considered tertiary structure this is discussed in Chapter 24. 

Computer simulations are regularly performed of the energetics of protein structure and their interactions with ligands using potential energy functions for the forces described so far. The energy functions are of necessity simplifications, but they are calibrated on experimental data. A minimalist model uses equation 11.3.15... 

Secondary protein structures are the local regular and random conformations assumed by sections of the peptide chains found in the structures of peptides and proteins. The main regular conformations found in the secondary structures of proteins are the a-helix, the fl-pleated sheet and the triple helix (Figure 1.8). These and other random conformations are believed to be mainly due to intramolecular hydrogen bonding between different sections of the peptide chain. 

There are also strong hints that protein structures fulfil relations very similar to those reported for the RNA structures. In a recent paper [25] it was shown that the first regularity, the existence of a few common and many rare structures, is indeed observed with lattice protein models as well. Extensive neutrality seems to be present with proteins, as the data on the molecular clock of evolution derived lfom sequence comparisons show [1]. 

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