Structural domain

Protein folding remains a problem because there are 20 different amino acids tbat can be combined into many more different proteins tban there are atoms in the known universe. In addition there is a vast number of ways in which similar structural domains can be generated in proteins by different amino acid sequences. By contrast, the structure of DNA, made up of only four different nucleotide building blocks that occur in two pairs, is relatively simple, regular, and predictable. 

The fundamental unit of tertiary structure is the domain. A domain is defined as a polypeptide chain or a part of a polypeptide chain that can fold independently into a stable tertiary structure. Domains are also units of function. Often, the different domains of a protein are associated with different functions. For example, in the lambda repressor protein, discussed in Chapter 8, one domain at the N-terminus of the polypeptide chain binds DNA, while a second domain at the C-terminus contains a site necessary for the dimerization of two polypeptide chains to form the dimeric repressor molecule. 

When comparable amounts of oil and water are mixed with surfactant a bicontinuous, isotropic phase is formed [6]. This bicontinuous phase, called a microemulsion, can coexist with oil- and water-rich phases [7,1]. The range of order in microemulsions is comparable to the typical length of the structure (domain size). When the strength of the surfactant (a length of the hydrocarbon chain, or a size of the polar head) and/or its concentration are large enough, the microemulsion undergoes a transition to ordered phases. One of them is the lamellar phase with a periodic stack of internal surfaces parallel to each other. In binary water-surfactant mixtures, or in... 

Now that many thousands of proteins have been sequenced (more than 100,000 sequences are known), it has become obvious that certain protein sequences that give rise to distinct structural domains are used over and over again in modular fashion. These protein modules may occur in a wide variety of pro-... 

Lu J, Sista P, Giguel F, Greenberg M, Kuritzkes DR (2004) Relative replicative fitness of human immunodeficiency virus type 1 mutants resistant to enfuvirtide (T-20), J Virol 78 4628 637 Lu M, Blacklow SC, Kim PS (1995) A tiimeric structural domain of the HlV-1 transmembrane glycoprotein, Nat Struct Biol 2 1075-1082... 

Tertiary structure concerns the relationships between secondary structural domains. Quaternary structure of proteins with two or more polypeptides (oligomeric proteins) is a feature based on the spatial relationships between various types of polypeptides. 

And third, since virtually all enzymes [67], particularly those that catalyze phos-phoryl-transfer reactions [68 74], possess structures with at least two, discrete, relatively rigid structural domains, or lobes, separated by a deep cleft, the cytoplasmic portion of the H -ATPase polypeptide chain in the model of Fig. 2 is drawn in such a way as to suggest this situation. The proposed interdomain cleft is indicated by the arrow. No additional structural features of the ATPase molecule are implied in the model. In regard to comparisons with the Ca -ATPase, it is of interest to note that the two cytoplasmic domains proposed in Fig. 2 correspond to the Cl and C2 domains in the model of Andersen and Vilsen [53]. 

The concept that different structural domains on the heparin chains are principally involved for optimal activity in the foregoing interactions could not be perceived in early work on structure-activity correlations, because the activity of heparin has been most frequently evaluated only with whole-blood-clotting tests (such as the U.S.P. assay). Development of assays for specific clotting-factors (especially Factor Xa and thrombin) has permitted a better insight into the mechanism of action of heparin at different levels of the coagulation cascade. 

FIGURE 7.5 Structural domains of LHCII xanthophylls. Aromatic amino acids tyrosine in the neoxanthin domain and tryptophan and phenylalanine in the violaxanthin domain are labeled as Y, W, and F, respectively. 

Buck K., Amara S. Chimeric dopamine-norepinephrine transporters delineate structural domains influencing selectivity for catecholamines and l-methyl-4-phenylpyridinium. Proc. Natl. Acad. Sci. U.S.A. 91 12584, 1994. 

Figure 1. (a) A schematic representation of the overall organization of the molecule of human ceruloplasmin. Domains 2,4, and 6 contain mononuclear copper centers, while the trinuclear copper cluster is located at the interface of domains 1 and 6. (b) An a-carbon ribbon diagram of the human ceruloplasmin molecule viewed along the pseudo threefold axis highlighting the triplication of the structure. Domains 1, 3, and 5 are depicted by striped motifs, whereas domains 2, 4, and 6 are dark shaded. The copper... 

Figure 7. Traces of the a-carbon polypeptide backbone of domains 1 and 6 in the hCP structure. Domain 1 is shown (shaded) on the left hand side of the diagram this domain contributes four histidine residues (not shown) to the trinuclear cluster copper atoms are depicted as black spheres. Domain 6 is on the right hand side of the figure and also contributes four histidine residues to the cluster. The portion of the polypeptide chain colored black is that which is missing in the truncated enzyme. This polypeptide, residues 991 to 1046 inclusive, includes two histidine residues bound to the trinuclear copper center and three residues bound to the mononuclear copper in domain 6 these residues are depicted in black. The absence of the C-terminal polypeptide would also remove over 50% of the interdomain hydrogen-bond and iron-pair interactions observed in the intact enzyme.

Each CHS monomer consists of two structural domains (Fig. 12.5, left). The upper domain exhibits the a-p-a-p-a pseudo-symmetric motif observed in fatty acid P-ketoacyl synthases (KASs) (Fig. 12.5, right).20 Both CHS and KAS use a cysteine as a nucleophile in the condensation reaction, and shuttle reaction intermediates via CoA thioester-linked molecules or ACPs, respectively. The conserved architecture of the upper domain maintains the three-dimensional position of the catalytic residues of each enzyme Cysl64, His303, and Asn336 in CHS correspond to a Cys, His, and His in KAS I and II. 

Buck, K. J. and Amara, S. G. (1995) Structural domains of catecholamine transporter chimeras involved in selective inhibition by antidepressants and psychomotor stimulants. Mol. Pharmacol. 48,1030-1037. 

The association of secondary structures to give super-secondary structures, which frequently constitute compactly folded domains in globular proteins, is completed by the a-a motifs in which two a-helices are packed in an anti-parallel fashion, with a short connecting loop (Figure 4.8c). Examples of these three structural domains, often referred to as folds, are illustrated in Figures 4.9—4.11. The schematic representation of the main chains of proteins, introduced by Jane Richardson, is used with the polypeptide backbone... 

The precise structure subset, dendrimers are prepared using iterative protection-condensation-deprotection reaction cycles. These reiterative cycles incorporate ABn monomers (i.e. branch cell units) into structural domains referred to as dendrons. Assembly of these dendrons can proceed in a divergent [1] (core... 

H41. Huby, T., Doucet, C., Dieplinger, H., Chapman, J., and Thillet, J., Structural domains of apolipoprotein(a) and its interaction with apolipoprotein Bl00 in the lipoprotein(a) particle. Biochemistry 33, 3335-3341 (1994). 

Another distinction between protein domains are continuous and discontinuous domains. A continuous domain has a consecutive region of peptide that folds up to form a single domain all the examples in Fig. 2 are continuous domains. Discontinuous domains are composed of non-consecutive regions of the peptide to form a single domain. It is not obvious that discontinuous domains, unlike continuous domains, can exist in isolation. From known structures it has been shown that slightly less than one third of structural domains are discontinuous (Jones et al., 1998). 

PAC Motif C-terminal to PAS motifs (likely to contribute to PAS structural domain) E(MFP)AB 0(0) 5(5) 2ARN... 

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