Multisubunit complexes

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. 

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. 

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. 

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... 

A well-studied example is that of IkB kinase (IKK) which mainly transduces signals that activate the transcription factor NF-kB. IKK is a multisubunit complex that contains four different subunits IKK-1 (also known as IKKa), IKK-2 (lKK/3), a regulatory subunit called NEMO (also known as IKK7), and an additional subunit critical for substrate targeting called ELKS (because it is rich in glutamate [E], leucine [L], lysine [K], and serine... 

Multiubiquitination of intracellular proteins is a prerequisite for the selective degradation of intracellular proteins by the ubiquitin-dependent proteolytic pathway [236,237]. Monoubiquitinated histones are not degraded by the protea-some [238,239]. Proteasome, a multisubunit complex that catalyzes both ubiquitin-dependent and ubiquitin-independent protein degradation, is found in the cytoplasm and nucleus [240-242]. Thus, it is possible that multiubiquitination of the histones may tag these proteins for degradation. 

Peterson, C.L., Dingwall, A., and Scott, M.P. (1994) Five SWI/SNF subunits are components of a large multisubunit complex required for transcriptional enhancement. Proc. Natl. Acad. Sci. USA 91, 2905-2908. 

Transporting ATP synthase [EC 3.6.1.34] in plants, also referred to as chloroplast ATPase and CFiCFo-ATPase, catalyzes the hydrolysis of ATP to produce ADP and orthophosphate. When coupled with proton transport the reverse reaction results in the synthesis of ATP by this multisubunit complex. CFi, isolated from the rest of the membrane-bound complex, retains the ATPase activity but not the proton-translocating activity. 

The formation of multisubunit complexes (for example, protein complexes). Such complex formation is usually a cooperative phenomenon. 

The iron-sulfur proteins include small proteins that function as remarkably simple electron carriers and large multisubunit complexes with multiple activities. Although many of these enzymes function in electron transfer in bioener-getic or biosynthetic pathways, it has become clear that iron-sulfur proteins catalyze a broad array of reactions not always involving electron transfer. 

There are three types of restriction endonucleases, designated I, II, and III. Types I and HI are generally large, multisubunit complexes containing both the endonucle-... 

Mediators and coactivators. Transcriptional activators that act in a crude cell-free system often do not function with purified DNA, RNA polymerase, and the basal transcription factors as indicated in Eq. 28-5. Studies with yeast, Drosophila, and human cells revealed that additional large multisubunit complexes known as mediators are needed 272/346-348 A yeast mediator complex consists of 20 subunits.349-350b Many activator proteins bind to the DNA sequences known as enchancers, discussed in the next section. Mediator complexes may also interact with enhancer-bound activators. Individual proteins, such as the TAF subunits, that bind to and cooperate with activator proteins are often called coactivators.351... 

The multisubunit complexes of the respiratory chain. Complexes I (NADH dehydrogenase) and II (succinate dehydrogenase) transfer electrons from NADH and succinate to UQ. Complex III (the cytochrome bc complex) transfers electrons from UQH2 to cytochrome c, and complex IV (cytochrome oxidase), from cytochrome c to 02. The arrows represent paths of electron flow. NADH and succinate provide electrons from the matrix side of the inner membrane, and 02 removes electrons on this side. Cytochrome c is reduced and oxidized on the opposite side of the membrane, in the lumen of a crista or in the intermembrane space. 

The six-electron reduction of sulfite to sulfide is catalyzed by sulfite reductase, a multisubunit complex composed of a flavoprotein and a heme iron-sulfur protein. 

The most striking difference between DNA-binding proteins in prokaryotes and eukaryotes has to do with the symmetry of the interaction. In prokaryotes the binding proteins almost always interact in a symmetrical fashion with the DNA. In eukaryotes most of the cases that have been examined so far involve proteins that interact in an asymmetrical fashion with the DNA. In many cases the regulatory proteins interact in multisubunit complexes that contain nonidentical subunits. Four different types of structural motifs are discussed The homeodomain, the zinc finger, the leucine zipper, and the helix-loop-helix. 

Bacterial family C polymerases are the major chromosomal replicative enzyme (Kornberg and Baker, 1992). Like other replicative polymerases, the holoenzyme interacts with other proteins and forms a large multisubunit complex consisting of at least 10 subunits (Kornberg and Baker, 1992). The a-subunit contains the DNA polymerase activity that is tightly associated with the e-subunit, which contains a 3 -5 exonuclease activity (Kelman and O Donnell, 1995). 

Type II restriction-modification systems differ from their type I and type III counterparts in that the endonuclease and DNA methylase activities are conducted by two separate enzymes (not a single multisubunit complex). The restriction endonuclease cleaves both strands of the DNA duplex within a defined recognition sequence, while the companion DNA methylase methylates a specific base within the same recognition sequence. In contrast... 

Most of the targets of plant defensive compounds are proteins and indeed many plant defensive agents are also proteins. Accordingly it is useful to briefly outline the various types of proteins encountered. Most proteins are water soluble but some function associated with membranes. The membrane-bound proteins can be firmly embedded in the phospholipid bilayer of the membrane (intrinsic or integral proteins) or are less intimately associated (extrinsic or peripheral membrane proteins). As outlined above, proteins may be monomeric, multisubunit or associated with large multisubunit complexes. 

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