Multiple domains

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...

Wu L, LaRosa G, Kassam N, et al. Interaction of chemokine receptor CCR5 with its ligands multiple domains for HIV-1 gpl20 binding and a single domain for chemokine binding. J Exp Med 1997 186(8) 1373—1381. 

Recombinant DNA technology has also facilitated detailed study of cytokine receptors. Based upon amino acid sequence homology, receptors are usually classified as belonging to one of six known superfamilies (Table 8.3). Individual members of any one superfamily characteristically display 20-50 per cent homology. Conserved amino acids normally occur in discrete bands or clusters, which usually correspond to a discrete domain in the receptor. Most receptors exhibit multiple domains. In some cases a single receptor may contain domains characteristic of two or more superfamilies. For example, the IL-6 receptor contains domains characteristic of both the haematopoietic and immunoglobulin superfamilies, making it a member of both. 

The method can be used in combination with a multiple domain dissection procedure (Adams, et al., 1996) to construct a near full-length domain profile when the common domain is masked by the presence of other more conserved domains. 

Baida MS, Flores-Maldonado C, Cereijido M, and Matter K [2000] Multiple domains of occludin are involved in the regulation of paracellular permeability. J Cell Biochem 78 85-96... 

Fig. 12.3. Subclasses of the CUE domain family. All human and budding yeast members of the CUE family have been aligned and subjected to neighbor-joining dendrogram analysis. In proteins having multiple domains, the domain number is indicated in square...

Lopes JE, Torgerson TR, Schubert LA, Anover SD, Ocheltree EL, Ochs HD, Ziegler SF Analysis of FOXP3 reveals multiple domains required for its function as a transcriptional repressor. J Immunol 2006 177 3133-3142. 

Nicolas, R.H. and Goodwin, G.H. (1996) Molecular cloning of polybromo, a nuclear protein containing multiple domains including five bromodomains, a truncated HMG-box, and two repeats of a novel domain. Gene 175, 233-240. 

In this cooperative binding event, the Rcol-PHD finger is primarily responsible for providing affinity for nucleosomes, while the Eafi chromodomain contributes specificity for the methylated H3K36 mark [59, 60]. These examples demonstrate how multiple domains can cooperate to read a histone code with high fidelity and enhanced affinity. 

Yoon, C. H., C. Chang, N. A. Hopper, G. M. Lesa, and P. W. Sternberg. Requirements of multiple domains of SLI-I, a Caenorhabditis elegans homologue of c-Cbl, and an inhibitory tyrosine in LET-23 in regulating vulval differentiation. Mol Biol Cell. 11 4019-31.2000. 

Figure 10.2 Single molecule force-extension curve of three different types of molecules (a) a short chain or rigid tod molecule (b) a long chain polymer with multiple domains, such as titin, where bi-b represents the unfolding of individual domains and (c) a tegular random coil long chain. Adapted from Smith et al. (1999). Copyright 1999 Nature Publishing Group.

Figure 9 shows the convergence domain as well as steady-state multiplicity domain on fi, h plane. We can see that steady-state multiplicity is not generally... 

Figure 9 A convergence domain and steady-state multiplicity domain.

Clinical outcomes before, during and after treatments were assessed in six multiple domains represented by 19 separate measures. The domains were ADHD symptoms aggression-oppositional defiant disorder internalizing symptoms social skills parent child relations and cognitive performance (measured with three subscales of the Wechsler Individual Achievement test readmg, mathematics, spelling). 

Uhl, M.A. Miller, J.F. Integration of multiple domains in a two-component sensor protein the Bordetella pertussis BvgAS phosphorelay. EMBO J., 15, 1028-1036 (1996)... 

Polypeptides with more than a few hundred amino acid residues often fold into two or more stable, globular units called domains. In many cases, a domain from a large protein will retain its correct three-dimensional structure even when it is separated (for example, by proteolytic cleavage) from the remainder of the polypeptide chain. A protein with multiple domains may appear to have a distinct globular lobe for each domain (Fig. 4-19), but, more commonly, extensive contacts between domains make individual domains hard to discern. Different domains often have distinct functions, such as the binding of small molecules or interaction with other proteins. Small proteins usually have only one domain (the domain is the protein). 

Both enzymes and antibodies are proteins. Antibodies consist of subunits with multiple domains, just as do some enzymes. Both enzymes and antibodies have binding sites for small molecules between domains or subunits. In view of such similarities it isn t surprising that some antibodies have catalytic properties. The possibility was suggested in 1969 by Jencks 3 He also proposed that injection of a mouse with a hapten, that resembled a transition state for an enzyme, might induce formation of antibodies complementary to the transition-state structure. These might be catalytic. By the early 1980s such antibodies were discovered.1 d Some of the first catalytic antibodies (also dubbed abzymes) had esterase activity. The haptens used to induce antibody formation were phosphonates such as the following.e f... 

Liu Y, Oakeley EJ, Sun L, Jost JP. Multiple domains are involved in the targeting of the mouse DNA methyltransferase to the DNA replication foci. Nucleic Acids Res 1998 26 1038-1045. 

Multidomain Structures. Proteins may have multiple domains, but the different domains of these proteins have never been seen independently of each other, therefore accurate determination of their boundaries is not possible and perhaps not meaningful. 

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