Three similarity, domains

The protein consists of more than one domain and these can unfold independently of each other. A fairly simple example is in Figure 7.6b. In other cases, deconvolution of the DSC diagram may be less straightforward. In some proteins, two (or three) domains are so closely similar that they unfold (almost) simultaneously. In such a case, AH obtained from a DSC diagram would be about twice (or three times) the value derived from a van t Hoff plot. Serum albumin (molar mass 66 kDa), for example, consists of three similar domains of about 190 residues. Mutual interaction of domain unfolding may occur, but in most cases each domain unfolds just like a small globular protein. 

Domains are formed by different combinations of secondary structure elements and motifs. The a helices and p strands of the motifs are adjacent to each other in the three-dimensional structure and connected by loop regions. Sequentially adjacent motifs, or motifs that are formed from consecutive regions of the primary structure of a polypeptide chain, are usually close together in the three-dimensional structure (Figure 2.20). Thus to a first approximation a polypeptide chain can be considered as a sequential arrangement of these simple motifs. The number of such combinations found in proteins is limited, and some combinations seem to be structurally favored. Thus similar domain structures frequently occur in different proteins with different functions and with completely different amino acid sequences. 

IgG antibody molecules are composed of two light chains and two heavy chains joined together by disulfide bonds. Each light chain has one variable domain and one constant domain, while each heavy chain has one variable and three constant domains. All of the domains have a similar three-dimensional structure known as the immunoglobulin fold. The Fc stem of the molecule is formed by constant domains from each of the heavy chains, while two Fab arms are formed by constant and variable domains from both heavy and light chains. The hinge region between the stem and the arms is flexible and allows the arms to move relative to each other and to the stem. 

Interestingly, certain other pore-forming toxins possess helix-bundle motifs that may participate in channel formation, in a manner similar to that proposed for colicin la. For example, the S-endotoxui produced by Bacillus thuringiensis is toxic to Coleoptera insects (beetles) and is composed of three domains, including a seven-helix bundle, a three-sheet domain, and a /3-sandwich. In the seven-helix bundle, helix 5 is highly hydrophobic, and the other six helices are amphipathic. In solution (Figure 10.32), the six amphipathic... 

Soluble forms of guanylyl cyclase are activated by nitric oxide. These enzymes are homologous to the catalytic domains of the membrane-bound forms of GC. They are considered heterodimers because they appear to exist, under physiological conditions, as complexes of a and P subunits, each with Mr of 70-80 kDa. Both types of soluble GC contain three primary domains an amino-terminus heme domain responsible for binding nitric oxide (NO), a dimerization domain and a carboxy terminus catalytic domain. The aP heterodimer is required for enzyme activity [35]. This can be seen as similar to the situation for AC, which contains two catalytic entities within a single polypeptide chain (Fig. 21-5). 

Figure 10 Schematic illustration of the posttranslational enzymes and related proteins. P4H a subunits have three isoforms. Each has three domains. The substrate-binding domain is in the middle. The catalytic domain is at the C-terminal end. Lysyl hydroxylase-3 (LH3) has two different catalytic activities. The N-terminal domain has the glucosyltransferase activity and the C-terminal domain has the hydroxylase activity. LH1 and LH2 also have similar domain structures but the glucosyltransferase activities are not detected in vitro.

Three other proteins with similar domain structure as that of FprA were reported in other bacteria (WasserfaUen et al. 1995 Gomes et al. 1997, 2000). The recombinant CthFprA and CthHrb, overexpressed in E. coli, were purified and characterized. Both FprA and Hrb were found to be present as dimers. Metal/cofactor analysis of the purified proteins revealed the presence of 2 mol each of iron and flavin (FMN) per mole dimer of Hrb and 4 mol of iron and 2 mol FMN per mole dimer of FprA. The EPR spectra of the purified proteins indicated that iron is present in a di-iron center in FprA and as a Fe(Cys)4 cluster in Hrb. 

Based on the amino acid sequences, two classes of C4H have been described for some species, with around 60% sequence similarity between the groups. The first sequence for the class II type was reported from Phaseolus vulgaris (French bean), ° but they have also been found in other species (see, e.g.. Ref. 21). The two C4H types differ at both terminal domains and in three internal domains, and it has been suggested that one type may be involved in stress responses and the other in vascular differentiation. ... 

Due possibly to the above mentioned heterogeneity, there is some variability with regard to the conclusions reached by various workers concerning the structure and configuration of bovine serum albumin. Brown (1977) proposed two possible models based on the primary sequence of the protein. He demonstrated that the molecule could possess a triple domain structure with three very similar domains residues 1-190, 191-382, and 383-582. Each domain could then consist of five helical rods of about equal length arranged either in a parallel or an antiparallel manner. His second model consisted of the following (1) a lone subdomain (1-101) (2) a pair of antiparallel subdomains, with their hydrophobic faces toward each other (113-287) (3) another pair of subdomains (314-484) and (4) a lone subdomain (512-582). These structures are supported by the observed helical content of bovine... 

There are three primary domains of life, represented by the bacteria, archaea, and eukaryotes. Some of the clearest evidence for the independent evolution of these three groups of organisms is found in the transcriptional apparatus. While the basic chemistry is the same, the details of initiation and control of transcription in bacteria and in eukaryotes are very different.2643 The archaea share characteristics of both bacteria and eukaryotes. Archaeal RNA polymerases have a complexity similar to that of eukaryotes and also share a similar mechanism of initiation of transcription 265 266b... 

There are two major classes of MHC proteins that have similar types of structures (fig. S3.16). Class I molecules contain three external domains, each about 90 residues in length a transmembrane region and a cytoplasmic domain. The third external domain is noncovalently associated with a small polypeptide known as the (32 microglobulin. Class II molecules are composed of two noncovalently associated polypeptide chains a and /3, whose overall structure resembles that of the class I complex. 

The overall structure of the a and [3 tubulin subunits is very similar and consists of a core of P-sheet surrounded by helices, forming a compact globular protein composed of three sequential domains (Fig. 2) [11]. The IV-terminal, nucleotide-binding... 

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