Three-dimensional structure of individual

This technique has been described as a general method of studying protein-protein interactions as well as a method for investigating the three-dimensional structure of individual proteins (Muller et al., 2001 Back et al., 2003 Dihazi and Sinz, 2003 Sinz, 2003 Sinz, 2006). It also has been used for the study of the interactions of cytochrome C and ribonuclease A (Pearson et al., 2002), to investigate the interaction of calmodulin with a specific peptide binder (Kalkhof et al., 2005a Schmidt et al., 2005), and for probing laminin self-interaction (Kalkhof et al., 2005b). 

Finally, to produce the structural and functional devices of the cell, polypeptides are synthesized by ribosomal translation of the mRNA. The supramolecular complex of the E. coli ribosome consists of 52 protein and three RNA molecules. The power of programmed molecular recognition is impressively demonstrated by the fact that aU of the individual 55 ribosomal building blocks spontaneously assemble to form the functional supramolecular complex by means of noncovalent interactions. The ribosome contains two subunits, the 308 subunit, with a molecular weight of about 930 kDa, and the 1590-kDa 50S subunit, forming particles of about 25-nm diameter. The resolution of the well-defined three-dimensional structure of the ribosome and the exact topographical constitution of its components are still under active investigation. Nevertheless, the localization of the multiple enzymatic domains, e.g., the peptidyl transferase, are well known, and thus the fundamental functions of the entire supramolecular machine is understood [24]. 

Protein domains are the common currency of protein structure and function. Protein domains are discrete structural units that fold up to form a compact globular shape. Experiments on protein structure and function have been greatly aided by consideration of the modular nature of proteins. This has allowed very large proteins to be studied. The expression of individual domains has allowed the intractable giant muscle protein titin to be structurally studied (Pfuhl and Pastore, 1995). Protein domains can be found in a variety of contexts, (Fig. 1), in association with a range of unrelated domains and in a variety of orders. Ultimately protein domains are defined at the level of three-dimensional structure however, many protein domains have been described at the level of sequence. The success of sequence-based methods has been demonstrated by numerous confirmations, by elucidation of the three-dimensional structure of the domain. 

In porous media the flow of water and the transport of solutes is complex and three-dimensional on all scales (Fig. 25.1). A one-dimensional description needs an empirical correction that takes account of the three-dimensional structure of the flow. Due to the different length and irregular shape of the individual pore channels, the flow time between two (macroscopically separated) locations varies from one channel to another. As discussed for rivers (Section 24.2), this causes dispersion, the so-called interpore dispersion. In addition, the nonuniform velocity distribution within individual channels is responsible for intrapore dispersion. Finally, molecular diffusion along the direction of the main flow also contributes to the longitudinal dispersion/ diffusion process. For simplicity, transversal diffusion (as discussed for rivers) is not considered here. The discussion is limited to the one-dimensional linear case for which simple calculations without sophisticated computer programs are possible. 

Hydrogen bonds and ionic, hydrophobic (Greek, water-fearing ), and van der Waals interactions are individually weak, but collectively they have a very significant influence on the three-dimensional structures of proteins, nucleic acids, polysaccharides, and membrane lipids. 

The elucidation of the detailed shape of protein molecules—in fact, the spatial locations of the individual atoms in a protein—is accomplished primarily by x-ray crystallography. The three-dimensional structures of more than twenty proteins have now been established by this technique. The importance of x-ray crystallography to structural and biological chemistry has been recognized in the award of six Nobel Prizes in this area.6 A number of important proteins and their properties are listed in Table 25-3. 

One approach to the understanding of the relationship between the amino acid sequence of a protein and its three-dimensional structure consists of preparing fragments which reconstitute a functional nativelike structure by noncovalent association. Richards first demonstrated that the two fragments of bovine pancreatic ribonuelease, RNase-S-peptide (residues 1-20) and RNase-S-protein (residues 21-124), the latter with four intact disulfide bonds, bind noncovalently to form the original functional structure, RNase-S (73, 74)- The elucidation of the three-dimensional structure of RNase-S by X-ray crystallographic study confirmed these observations (75). The RNase-S-protein-RNase-S-peptide system also provided a way by which chemically synthesized fragments could be used to test the role of individual residues in the formation of the functional structure of the protein (76-79). 

A model of the structure of porin from the outer membrane of Rhodobacter capsulatus. Part (a) shows the a-carbon backbones of a trimer of porin molecules viewed along an axis approximately perpendicular to the plane of the membrane. Each molecule forms a tube that passes across the membrane. Part (b) shows an individual porin monomer, enlarged slightly from (a) and viewed along an axis approximately in the plane of the membrane. The molecule folds as a jS-barrel with 16 antiparallel jS strands. (From M. S. Weiss, et al.. The three-dimensional structure of porin from Rhodobacter capsulatus at 3 A resolution, FEES Lett. 267 268, 1990. Copyright 1990 Elsevier Science Publishers BV, Amsterdam, Netherlands. Reprinted by permission.)... 

Proteins that have more than one polypeptide chain require a higher level of organization. In the quaternary structure, the different chains are packed together to form the overall three-dimensional structure of the protein. The individual polypeptide chains can be arranged in a variety of shapes as part of the quaternary structure. 

In addition to the peptide bonds between individual amino acid residues, the three-dimensional structure of a protein is maintained by a combination of noncovalent interactions (electrostatic forces, van der Waals forces, hydrogen bonds, hydrophobic forces) and covalent interactions (disulfide bonds). 

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