Multisubunit

The DNA part of each control module can be divided into three main regions, the core or basal promoter elements, the promoter proximal elements and the distal enhancer elements (Figure 9.1). The best characterized core promoter element is the TATA box, a DNA sequence that is rich in A-T base pairs and located 25 base pairs upstream of the transcription start site. The TATA box is recognized by one of the basal transcription factors, the TATA box-binding protein, TBP, which is part of a multisubunit complex called TFIID. This complex in combination with RNA polymerase 11 and other basal transcription factors such as TFIIA and TFIIB form a preinitiation complex for transcription. 

No region of the cytochrome penetrates the membrane nevertheless, the cytochrome subunit is an integral part of this reaction center complex, held through protein-protein interactions similar to those in soluble globular multisubunit proteins. The protein-protein interactions that bind cytochrome in the reaction center of Rhodopseudomonas viridis are strong enough to survive the purification procedure. However, when the reaction center of Rhodohacter sphaeroides is isolated, the cytochrome is lost, even though the structures of the L, M, and H subunits are very similar in the two species. 

ITowever, membrane proteins can also be distributed in nonrandom ways across the surface of a membrane. This can occur for several reasons. Some proteins must interact intimately with certain other proteins, forming multisubunit complexes that perform specific functions in the membrane. A few integral membrane proteins are known to self-associate in the membrane, forming large multimeric clusters. Bacteriorhodopsin, a light-driven proton pump protein, forms such clusters, known as purple patches, in the membranes of Halobacterium halobium (Eigure 9.9). The bacteriorhodopsin protein in these purple patches forms highly ordered, two-dimensional crystals. 

Rieske proteins are constituents of the be complexes that are hydro-quinone-oxidizing multisubunit membrane proteins. All be complexes, that is, bci complexes in mitochondria and bacteria, b f complexes in chloroplasts, and corresponding complexes in menaquinone-oxidizing bacteria, contain three subunits cytochrome b (cytochrome 6e in b f complexes), cytochrome Ci (cytochrome f in b(,f complexes), and the Rieske iron sulfur protein. Cytochrome 6 is a membrane protein, whereas the Rieske protein, cytochrome Ci, and cytochrome f consist of water-soluble catalytic domains that are bound to cytochrome b through a membrane anchor. In Rieske proteins, the membrane anchor can be identified as an N-terminal hydrophobic sequence (13). 

The group of the be complexes comprises bci complexes in mitochondria and bacteria and bef complexes in chloroplasts. These complexes are multisubunit membrane proteins containing four redox centers in three subunits cytochrome b (cytochrome be in bef complexes) comprising two heme b centers in a transmembrane arrangement, cyto-... 

The cis-acting elements that decrease or repress the expression of specific genes have also been identified. Because fewet of these elements have been smdied, it is not possible to fotmulate genetalizations about their mechanism of action—though again, as for gene activation, chromatin level covalent modifications of histones and other proteins by (repressor)-recruited multisubunit corepressors have been imphcated. 

Isolation and purification of the multisubunit dihydropyridine-sensitive Ca channels from skeletal muscle... 

The purified L-type channels from skeletal muscle appear to be a multisubunit protein containing the products of four different and unrelated genes. A cartoon depicting some of the features of the purified protein is shown in Fig. 1. The subunits of the channel are commonly referred to as the ai, a2, ]8, y, and 8. These have been observed to migrate in a variety of SDS-polyacrylamide gels with apparent... 

Fig. 2 Illustration of protein structure levels. Shown are primary structure (amino acid sequence), secondary structure (local order of protein chain, a-helix shown as an example), tertiary structure (assembly of secondary structure elements), and quaternary structure (relationship of different protein chain in multisubunit protein). (From Ref. 66.)...

As was mentioned earlier, DAG activates protein kinase C, which phosphorylates transcription factors like NFjcB nuclear transcription factor. NFjcB forms a multisubunit complex with an inhibitory subunit which is phosphorylated by PKC. The complex disintegrates and what is released translocates to the nucleus and initiates gene transcription. NFjcB is a heterodimer, with two distinct DNA-binding subunits 50 kDa and 65 kDa, both being members of the Rel transcription factor family. These proteins have an important role in the signaling cascade of the cellular defense system, and activate numerous genes in response to pathogens or inflammatory cytokines. 

ING Inhibitor of growth. A family of tumour suppressors (INGl-5). ING3, 4 and 5 are found in multisubunit complexes with the Tip60, MOZ/MORF and HBOl MYST HATs. Function in a number of key cellular processes and are frequently inactivated in human cancer. 

NuA4 Nucleosome acetyl transferase of histone H4. A multisubunit complex which includes, notably, TRRAP, p400 and Tip60 proteins. 

While all MYST family members possess intrinsic HAT activity, they do not function in isolation in vivo but, rather, are found in multisubunit protein complexes. Thus, to fully understand or to plausibly speculate about the potential roles of MYST HATs in disease, it is necessary to incorporate the known facts about other complex members. To this end, the sections of this chapter that discuss individual MYST HATs will also describe the complexes within which they function and summarize the available disease-related information about other complex components. 

Yamaguchi Y, Takagi T, Wada T, Yano K, Euruya A, Sugimoto S, Hasegawa J, Handa H (1999) NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation. Cell 97 41-51... 

Tersteegen, A. and Hedderich, R. (1999) Methanobacterium thermoautotrophicum encodes two multisubunit membrane-bound [NiFe] hydrogenases. Transcription of the operons and sequence analysis of the deduced proteins. Eur. J. Biochem. 264, 930-43. 

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