Folded polypeptide domains

The other noteworthy oxidoreductase system is the redox activity of polyethylene oxide modified cyt c in [EMIM][CF3MeS02l by optical waveguide spectroelectro-chemical analysis [109]. Cyt c was effectively dissolved in IL due to the polyethylene oxide side chains and found to be stable over a period of a month [109]. But the report also confirms that organic bulky ions in ILs do not offer any advantage rather are disadvantageous for electron transfer reactions of proteins having shielded cofactor inside the folded polypeptide domain since no cyclic voltammogram of polyethylene oxide coated cyt c was detected in IL. 

Protein structure determinations have identified several examples of one domain inserted within another. One example is the E. coli DsbA protein, which catalyzes the formation of disulfide bonds in the periplasm. The enzyme consists of two domains a thioredoxin-like domain that contains the active site, and an inserted helical domain similar to the C-terminal domain of thermolysins (Martin et al., 1993). The inserted domain forms a cap over the active site, suggesting that it plays a role in binding to partially folded polypeptide chains before oxidation of... 

The aaRSs possess diverse polypeptide domains and insertions, in addition to their catalytic core. Likely, these domains evolved to enhance specificity and fidelity and, in some cases, confer other functions (4, 5). One such domain is the C-terminal anticodon-binding domain that is widely varied (1). For example, GluRS and GlnRS have highly conserved active sites within their canonical aminoacylation cores but have appended N-terminal anticodon-binding domains that are composed primarily of either a-helices or fS-strands, respectively. In addition, common RNA-binding protein domains such as the OB-fold have been incorporated into aaRSs such as LysRS-II. In at least half of the aaRSs, an internal or appended domain confers amino acid editing activity (3). 

Also see color figure.) Tissue factor-factor Vila complex. The three-dimensional structure of the complex of factor Vila and tissue factor (minus the transmembrane polypeptide domain of the tissue factor) in the absence of membrane surface. It is approximately 115 A in length and has a diameter of 40-50 A. Factor Vila shows its four distinct domains the Gla domain, two EGF-like domains, and the proteinase domain. Tissue factor contacts factor VHa via the interface between the two fibronectin type Ill-like domains. All four domains of factor Vila appear to be involved in the interaction between tissue factor and factor Vila. The Gla domain of factor Vila is folded very similarly to the Gla domain of prothrombin (Gla domain of prothrombin fragment 1). Activation of factor VII can be catalyzed by thrombin, factor Xa, factor Vila, and factor Xlla—all by cleavage at Arg -Ile . Secondary structures are shown in the center diagram two views of the close interactions between TF and factor Vila are shown in the two diagrams at each side. 

Lutz Riechmann and Greg Winter, Novel folded protein domains generated by combinatorial shuffling of polypeptide segments, Proceedings of the National Academy of Sciences USA, 97 (2000), 10068-10073. 

Quantitatively, tertiary interactions fold polypeptide chains into one or several domains to form compact globular structure. Their compactness, which characterizes domains, can be expressed as the ratio of their surface area to the surface area of a sphere versus the same volume with an observed values of 1.64 0.08. Thus the domain concerns a polypeptide chain or a part of a polypeptide chain that can independently fold into compact, stable tertiary structure. 

Tertiary structure describes the ultimate three-dimensional conformation of a folded polypeptide chain. Major elements of tertiary structure typically involve longer range backbone interactions various elements of secondary structure are associated, resulting in the formation of structural or functional domains, and the amino acid side chains are packed in a well-defined manner. The side chains may stabilize the protein structure through a variety of interactions, including the formation of cystinyl disulfide bonds (Figure 7). 

Domain Sequence of a polypeptide chain that can independently fold into a stable three-dimensional structure... 

Fig. 5. Protein folding. The unfolded polypeptide chain coUapses and assembles to form simple stmctural motifs such as -sheets and a-hehces by nucleation-condensation mechanisms involving the formation of hydrogen bonds and van der Waal s interactions. Small proteins (eg, chymotrypsin inhibitor 2) attain their final (tertiary) stmcture in this way. Larger proteins and multiple protein assembhes aggregate by recognition and docking of multiple domains (eg, -barrels, a-helix bundles), often displaying positive cooperativity. Many noncovalent interactions, including hydrogen bonding, van der Waal s and electrostatic interactions, and the hydrophobic effect are exploited to create the final, compact protein assembly. Further stmctural...

Figure 2.11 Beta sheets are usuaiiy represented simply by arrows in topology diagrams that show both the direction of each (3 strand and the way the strands are connected to each other along the polypeptide chain. Such topology diagrams are here compared with more elaborate schematic diagrams for different types of (3 sheets, (a) Four strands. Antiparallel (3 sheet in one domain of the enzyme aspartate transcarbamoylase. The structure of this enzyme has been determined to 2.8 A resolution in the laboratory of William Lipscomb, Harvard University, (b) Five strands. Parallel (3 sheet in the redox protein flavodoxin, the structure of which has been determined to 1.8 A resolution in the laboratory of Martha Ludwig, University of Michigan, (c) Eight strands. Antiparallel barrel in the electron carrier plastocyanln. This Is a closed barrel where the sheet is folded such that (3 strands 2 and 8 are adjacent. The structure has been determined to 1.6 A resolution in the laboratory of Hans Freeman in Sydney, Australia. (Adapted from J. Richardson.)...

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