Domain organisation

Figure 2. Domain organisation, three-dimensional structure and sequence-into-colour translation of human coronin-lC. Top, True to scale schematic of the domain structure of human coronin-lC N, N-terminal coronin-specific signature, PI-7, p-propeller blades, C, unique C-terminal region, CC, coiled coll. Middle, top and side view of the structural homology model of human coronin-1 C, based on the crystal structure of human coronin-IA. p-propeller blades 1 and 2 that represent an unconventional and a typical p-propeller blade, respectively, are oriented to the bottom (left) and to the front (right). See also Chapter 5 by Bernadette McArdle and Andreas Hofmann. Figure 2 legend continued on the next page.

Figure 1. Domain organisation of coronins. Mapped binding sites for yeast coronin (crnip), as well as mammalian coronins 1 (1A), 2 (IB) and 3 (1C) are indicated.

The structures of a number of P-type ATPases, including the Na+-K+-ATPase, have been determined. They have a common overall domain organisation of the main catalytic (a-) subunit (Figure 9.10) six to twelve... 

Fig. 2. Predicted domain organisation of the DEBS Proteins. Ketoacyl Synthase (KS) Acyl Transferase (AT) Dehydratase (DH) Enoyl Reductase (ER) Keto Reductase (KR) Acyl Carrier Protein (ACP) Thioesterase (TE). Each domain is represented by a box with coded shading whose length is proportional to the size of the domain (KR) indicates an inactive KR domain. The ruler indicates the residue number within the primary structure of the constituent proteins. Linker regions are shown in proportion...

Figure 2.7 Domain organisation of erythromycin polyketide synthase. Gene sequence putative domains are represented as circles and the structural residues are ignored. Each module incorporates the essential KS, AT andACP domains, while all but one include optional reductive activities (KR, DH, ER). The one-to-one correspondence between domains and biosynthetic transformations explains how programming is achieved in this modular PKS. DEBS—deoxyerythronolide B synthase (reproduced with permission of Prof. James Staunton)...

Relatively recently a class of modular type 1 PKSs have been discovered which do not conform to the textbook colinearity rules [15]. In these particular systems, the domain organisation rarely correlates with the polyketide product due to the high diversity of non-canonical modules that often contain novel enzymatic domains. The most noticeable feature of these clusters, however, is the absence of integral AT domains within the PKS. Instead, the AT activity is supplied by a reduced number of free-standing enzymatic domains servicing every module in the entire cluster (Fig. 1.9) [25]. These systems are therefore termed trans-AT PKSs, of which the pederin PKS is an example (Fig. 1.10) [26]. In contrast, the 6-dEB system is an example of a c -AT PKS, where the AT domains are integral to the PKS, with an AT domain within each module (Fig. 1.8). 

In recent years the structural understanding of type I PKSs has developed significantly. In 2002 electron microscopy revealed the quaternary structure of the dimeric metazoan FAS, appearing to form a sideways H oiganisation (Fig. 1.28a) [93]. However, whether the homodimer formed in the FAS was organised in a head-to-head or head-to-tail fashion r ained unknown until 2006 when a 4.5 A crystal structure of the porcine FAS was solved (PDB 2VZ9), which confirmed the head-to-head model for domain organisation of the FAS (Fig. 1.28b) [94]. Around the same time, crystal stractures of a KS-AT didomain and a KR domain from the... 

Figure 3.2. Structure of some G-protein-linked receptors of the rhodopsin superfamily (a) the structural organisation of the predicted hydrophilic and hydrophobic domains of the receptor (b) how the hydrophilic regions form extracellular and intracellular loops, being anchored by the seven hydrophobic transmembrane domains.

The small subunit is composed of two domains. The N-terminal domain shows the characteristic architecture of flavodoxin with the phosphate moiety of the flavin cofactor occupying the binding pocket of the proximal [4Fe-4S] cluster. This N-terminal domain, including the proximal cluster, is found in all [NiFe] hydrogenases and is consequently an essential feature, both structural and functional, of these enzymes. By contrast, the C-terminal domain that binds the other [FeS] clusters is less organised and more variable in [FeS] cluster content and amino acid sequence. 

Limited proteolysis (Solomonson et al., 1986 Kubo et al., 1988 Notton et al., 1989) and radiation inactivation experiments (Solomonson et al., 1987) have shown that NR is organised in functional domains, as initially suggested by Brown et al. (1981). Each of the prosthetic groups is held in one of three catalytic domains which are linked one to another by protease sensitive hinges. Intersubunit interactions occur via the MoCo domain. After cleavage of either of the two hinges, NADH NR activity is lost but each domain, or pair of domains, retains its specific functional redox properties. This approach has revealed that each of the partial enzymatic activities of NR can be ascribed to one specific domain, or to... 

Baldock, C., Sherrat, M. J., Shuttleworth, C. A., and Kielty, C. M. (2003). The super-molecular organisation of collagen VI microfibrils. J. Mol. Biol. 330, 297-307. Bogin, O., Kvansakul, M., Rom, E., Singer, J., Yayon, A., and Hohenester, E. (2002). Insight into Schmid metaphyseal chondrodysplasia from the crystal structure of the collagen X NCI domain trimer. Structure 10, 165-173. 

The technique of molecular imprinting was successfully used to create a polymer with specific recognition sites. [9] A template was used to organise monomers during the polymerisation process. After the polymerisation, it was washed away from the insoluble network, leaving behind domains of complementary size and shape (Scheme 10). 

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