Class domains

Figure 5.3 Example of the discrimination of different modes of action based on testing with a battery of specific in vitro assays. The overlap of class domains indicates the ambiguity of assignments for chemicals with multiple modes of action. NST = non-specific toxicants DC = uncouplers PS = inhibitors of photosynthesis AChE = AChE inhibitors RA = reactive compounds SH = SH blocker RB = respiratory blocker. Reproduced from Nendza, Wenzel and Wienen (1995) with permission from Gordon and Breach Publishers, Lausanne.

Once proteins are divided into domains the domains are then classified hierarchically. At the top of the classification we usually find the class of a protein domain, which is generally determined from its overall composition in secondary structure elements. Three main classes of protein domains exist mainly a domains, mainly (3 domains, and mixed a p domains (the domains in the a — p class are sometimes subdivided into domains with alternating a/p secondary structures and domains with mixed a + p secondary structures). In each class, domains are clustered into folds according to their topology. A fold is determined from the number, arrangement, and connectivity of the domain s secondary structure elements. The folds are subdivided into superfamilies. A superfamily contains protein domains with similar functions, which suggests a common ancestry, often in the absence of detectable sequence similarity. Sequence information defines families, i.e., subclasses of superfamilies that regroup domains whose sequences are similar. 

As has been shown previously [243], both sets can be described by eigenvalue equations, but for the set 2 it is more direct to work with projectors Pr taking the values 1 or 0. Let us consider a class of functions/(x), describing the state of the system or a process, such that (for reasons rooted in physics)/(x) should vanish for X D (i.e., for supp/(x) = D, where D can be an arbifiary domain and x represents a set of variables). If Pro(x) is the projector onto the domain D, which equals 1 for x G D and 0 for x D, then all functions having this state property obey an equation of restriction [244] ... 

It should be emphasized at this point that the basic requirements of compatibility and consistency of finite elements used in the discretization of the domain in a field problem cannot be arbitrarily violated. Therefore, application of the previously described classes of computational grids requires systematic data transfomiation procedures across interfaces involving discontinuity or overlapping. For example, by the use of specially designed mortar elements necessary communication between incompatible sections of a finite element grid can be established (Maday et ah, 1989). 

Now consider a domain fl containing a surface Tc, whose properties are described in Section 1.1.7. Denote Sc = Tc clTc, flc = fl Tg. Introduce the unit normal n to Tc and define the opposite faces T of the surface Tg. The signs fit positive and negative directions of n, respectively. Then we denote the boundary of flc by dflc = T U T. We assume that there exists a closed extension S of Tc dividing the domain fl into two subdomains Di, D2 with boundaries dfli,dfl2 and such that Tc C S. It is assumed that = S , 80,2 = S+ U r. We say that the boundary dOc belongs to the class if 80,1,80,2 belong to G . ... 

For k = 1, the smoothness class of the boundary dflc can be reduced to Proof. Assume that S is the closed extension of Sc from the class dividing fl into two domains as before. The boundaries dfli,dfl2... 

Let a solid occupy the domain C B with the crack Sc such that its boundary dflc belongs to the class in accord with Section 1.4.1. Introduce the space... 

This class of smart materials is the mechanical equivalent of electrostrictive and magnetostrictive materials. Elastorestrictive materials exhibit high hysteresis between strain and stress (14,15). This hysteresis can be caused by motion of ferroelastic domain walls. This behavior is more compHcated and complex near a martensitic phase transformation. At this transformation, both crystal stmctural changes iaduced by mechanical stress and by domain wall motion occur. Martensitic shape memory alloys have broad, diffuse phase transformations and coexisting high and low temperature phases. The domain wall movements disappear with fully transformation to the high temperature austentic (paraelastic) phase. 

Another class of DNA-binding proteins are the polymerases. These have a nonspecific interaction with DNA because the same protein acts on all DNA sequences. DNA polymerase performs the dual function of DNA repHcation, in which nucleotides are added to a growing strand of DNA, and acts as a nuclease to remove mismatched nucleotides. The domain that performs the nuclease activity has an a/P-stmcture, a deep cleft that can accommodate double-stranded DNA, and a positively charged surface complementary to the phosphate groups of DNA. The smaller domain contains the exonuclease active site at a smaller cleft on the surface which can accommodate a single nucleotide. 

Thermoplastic Elastomers. These represent a whole class of synthetic elastomers, developed siace the 1960s, that ate permanently and reversibly thermoplastic, but behave as cross-linked networks at ambient temperature. One of the first was the triblock copolymer of the polystyrene—polybutadiene—polystyrene type (SheU s Kraton) prepared by anionic polymerization with organoHthium initiator. The stmcture and morphology is shown schematically in Figure 3. The incompatibiHty of the polystyrene and polybutadiene blocks leads to a dispersion of the spherical polystyrene domains (ca 20—30 nm) in the mbbery matrix of polybutadiene. Since each polybutadiene chain is anchored at both ends to a polystyrene domain, a network results. However, at elevated temperatures where the polystyrene softens, the elastomer can be molded like any thermoplastic, yet behaves much like a vulcanized mbber on cooling (see Elastomers, synthetic-thermoplastic elastomers). 

Eortunately, a 3D model does not have to be absolutely perfect to be helpful in biology, as demonstrated by the applications listed above. However, the type of question that can be addressed with a particular model does depend on the model s accuracy. At the low end of the accuracy spectrum, there are models that are based on less than 25% sequence identity and have sometimes less than 50% of their atoms within 3.5 A of their correct positions. However, such models still have the correct fold, and even knowing only the fold of a protein is frequently sufficient to predict its approximate biochemical function. More specifically, only nine out of 80 fold families known in 1994 contained proteins (domains) that were not in the same functional class, although 32% of all protein structures belonged to one of the nine superfolds [229]. Models in this low range of accuracy combined with model evaluation can be used for confirming or rejecting a match between remotely related proteins [9,58]. 

Figure 4.1 Alpha/beta domains are found in many proteins. They occur in different classes, two of which are shown here (a) a closed barrel exemplified by schematic and topological diagrams of the enzyme trlosephosphate isomerase and (b) an open twisted sheet with helices on both sides, as in the coenzymebinding domain of some dehydrogenases. Both classes are built up from p-a-p motifs that are linked such that the p strands are parallel. Rectangles represent a helices, and arrows represent p strands in the topological diagrams, [(a) Adapted from J. Richardson, (b) Adapted from B. Furugren.j...

The prolactin receptor, PER, which regulates milk production in mammals, belongs to the same receptor class as the growth hormone receptor. In addition to binding the hormone prolactin, PER also binds and is activated by growth hormone. The extracellular domain of PER forms a very stable 1 1 complex with growth hormone in solution this complex has been crystallized and its structure determined (Figure 13.21). We shall compare this structure with the 1 2 complex of the same hormone with GHR. 

Proteins are usually separated into two distinct functional classes passive structural materials, which are built up from long fibers, and active components of cellular machinery in which the protein chains are arranged in small compact domains, as we have discussed in earlier chapters. In spite of their differences in structure and function, both these classes of proteins contain a helices and/or p sheets separated by regions of irregular structure. In most cases the fibrous proteins contain specific repetitive amino acid sequences that are necessary for their specific three-dimensional structure. 

In this chapter we will discuss immunoglobulins of the IgG class, which is the major type of immunoglobulin in normal human serum, and which has the simplest structure. Each chain of an IgG molecule is divided into domains of about 110 amino acid residues. The light chains have two such domains, and the heavy chains have four. 

---