Structure of the functional domain

With the understanding of the characteristics of functional elements we developed in the previous sections, we can see that the functional domain is not just a collection of such elements, but that these characteristics introduce a structure into the domain. We have already encountered one aspect of this structure The functional domain consists of two disjoint parts, the real and the imaginary functional domain. We recall that a real element can be thought of as a system of 

In a very simplistic manner, we can visualise this as illustrated in Fig. C4.7. The two sets of parameters, X and Y, have the parameters of the irreducible element in common, and if the level of detail is reduced (i.e. X and Y become smaller), x and y will move towards the irreducible element. It is therefore clear that with the above definition, the distance between two real elements depends no only on the difference in functionality but also on the level of detail of the description. If we, for a moment, interpret Fig. C4.7 in the context of a particular project, then there will be one or more real elements that are complete, and we can visualise them as lying on the boundary of the real part of the functional domain, with the elements between them and the irreducible element being the included sets. 

The definition of distance between real functional elements, as illustrated by Fig. C4.7, reminds us that the parameters of a system are completely defined in terms of the parameters of its elements. It is true that a system consists of a set of elements and the interactions between them, and that as a result of these interactions the system can have properties not found in any of the elements, but the interactions have no independent existence, and they do not introduce any new parameters. The ability to interact must already be inherent in the elements that are interacting the system structure just describes which ones are active. It is this fact that allows us to associate a unique set in the parameter space of the imaginary part of the functional domain with a given system, as indicated in Fig. C4.7. However, more than one system may have the same parameter set they have different interactions between the same set of elements. 

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In addition to this large movement of the Rieske protein, small but nevertheless significant conformational differences within the functional domain are observed. The structure of the functional domain of the Rieske subunit in the PGi22 crystal form showing the ci positional state is the same as that of the water soluble fragment... 

A further feature of the structure of the functional domain arises from the central role of the irreducible element in the description of functionality and the definition of that element, as depicted in Fig. C4.4. Due to this view of an engineering project as an optimisation of the balance between cost and revenue, the secondary elements fall into two completely separate categories the elements describing aspects of the cost, and the elements describing aspects of the performance, as already mentioned at the end of Sec. C4.3 and illustrated in Fig. C4.6. 

Following on from the structure of the functional domain, real functional elements, as a system of imaginary elements, wiU also have certain structural features. To see how this comes abouL consider a particular project and develop, at firsL the plant s capability, i.e. what it must do, as a system of primary functional elements. The elements and structure of that system will, of course, depend both on the required capability and on our choice of functions to achieve it. However, once that system has been created, and we turn to describing the cost of providing the functions and the additional requirements on such aspects of the performance as reliability, maintainability, and safety, the corresponding elements refer to the primary elements. That is, the primary elements form what we might think of as a skeleton structure, and the secondary elements dress up this skeleton to form a real elemenL thereby inheriting some of the same structure. 

The overall structure of the variable domain is very similar to that of the constant domain, hut there are nine p strands instead of seven. The two additional p strands are inserted into the loop region that connects p strands C and D (red in Figure 15.8). Functionally, this part of the polypeptide chain is important since it contains the hypervariahle region CDR2. The two extra p strands, called C and C", provide the framework that positions CDR2 close to the other two hypervariahle regions in the domain structure (Figure 15.8). 

The class III deacetylases, named sirtuins, are structurally and functionally different from other HDACs. In contrast to the zinc-dependent deacetylation of classic HDACs, sirtuins depend on NAD" to carry out catalytic reactions. A variety of sirtuin crystal structures have been published over the past few years. The structures of human Sirt2 and SirtS as well as several bacterial Sir2 proteins could be derived, whereas no 3D structure is available for Sirtl and the other subtypes [69]. All solved sirtuin structures contain a conserved 270-amino-acid catalytic domain with variable N- and C-termini. The structure of the catalytic domain consists of a large classic Rossmann fold and a small zinc binding domain. The interface between the large and the small subdomain is commonly subdivided into A, B and C pockets. This division is based on the interaction of adenine (A), ribose (B) and nicotinamide (C) which are parts of the NAD" cofactor. (Figure 3.5) Whereas the interaction of adenine and... 

Fig. 5.2. Structural principles of transmembrane receptors, a) Representation of the most important functional domains of transmembrane receptors, b) Examples of subunit structures. Transmembrane receptors can exist in a monomeric form (1), dimeric form (2) and as higher oligomers (3,4). Further subunits may associate at the extracellular and cytosohc domains, via disulfide bridges (3) or via non-covalent interactions (4). c) Examples of structures of the transmembrane domains of receptors. The transmembrane domain may be composed of an a-hehx (1) or several a-helices linked by loops at the cytosolic and extracellular side (2). The 7-helix transmembrane receptors are a frequently occurring receptor type (see 5.3). Several subunits of a transmembrane protein may associate into an ohgomeric structure (3), as is the case for voltage-controUed ion channels (e.g., K channel) or for receptors with intrinsic ion channel function (see Chapter 17).

Fig. 7.13. Primary structure and oligomeric structure of CaM kinase II of type p. a) Linear representation of the functional domain of CaM kinase Up. b) The ohgomeric structure shown is proposed for an octamer of type P, based on electron microscopic investigations (Kanaseki et al., 1991). The iV-terminal catalytic domain is represented as a larger circle, the C-terminal ohgomerization domain by a smaller circle. CaM calmodulin.

Fig. 9.10. Domain structure of Raf kinase. Linear representation of the functional domains of c-Rafl kinase. CR control region.

With the 1 structure known, the functional domains of the enzyme can be more readily defined. By comparison with the proteolytic site of other serine active site proteases, it should be possible to deduce binding and catalysis functions that are common to serine proteases where structural homology is high, and to pursue the discovery of unique functions where homology is low. The structure of the carbohydrate binding domain can be compared with other fucose... 

The preceding sections highlighted the similarities and differences between the static crystal structure and the average solution structure of rhodopsin in the cytoplasmic domain. This section considers fluctuations in the structure of the cytoplasmic domain relative to the average. This is of interest, because dynamics sequences are often correlated with function, and that appears to be the case in rhodopsin. 

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