Protein modules

Small protein modules form adaptors for a signaling network... 

Pawson, T. Protein modules and signaling networks. Nature 373 573-580, 1995. 

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-... 

FIGURE 6,37 Ribbon structures of several protein modules utilized in the construction of... 

FIGURE 6.38 A sampling of proteins that consist of mosaics of individual protein modules. The modules shown include 7CG, a module containing 7-carboxyglutamate residues G, an epidermal growth-factor-like module K, the kringle domain, named for a Danish pastry ... 

FIGURE 23.22 The metabolic effects of insulin. As described in Chapter 34, binding of insulin to membrane receptors stimulates the protein kinase activity of the receptor. Subsequent phosphorylation of target proteins modulates the effects indicated. 

Interferon beta-la (AVONEX , Rebif ), interferon beta-lb (Betaferon ), and interferon beta (Fiblaferon ) are applied in multiple sclerosis to reduce both frequency and severity of disease incidents and for the treatment of severe viral infections. In multiple sclerosis, DFN- 3 proteins modulate the destruction of myelin in the cause of the autoimmune reaction. 

Heptahelical domains are protein modules found in all known G-protein coupled receptors, made up of seven transmembrane helices interconnected by three extra and three intracellular loops. For most G-protein coupled receptors activated by small ligands, the binding site is located in a cavity formed by transmembrane domains 3, 5, 6 and 7. 

FIG. 20 DNA duplex 20 used for studies regarding the protein-modulated DNA electron transfer. Methyltransferase M.Hhal is capable of binding to the shadowed recognition site between two oxidizable 5 -GG-3 sites (outlined letters). The complementary strand of the duplex contains the Rh intercalator, [Rh(phi)2bpy ], at its 5 end, which can function as a photooxidant. (Adapted from Ref. 168.)... 

Benfanati, F, Onofri, F and Giovedi, S (1999) Protein-protein interactions and protein modules in the control of transmitter release. Phil. Trans. Roy. Soc. Lond. B 354 243-257. 

It is perhaps not surprising that DA produces such mixed effects. The Di receptor is primarily linked to the activation of adenylate cyclase and then protein kinase A. The response to its activation will therefore depend on the ion channels and other proteins modulated by the kinase which can vary from one neuron to another. Since the D2 receptor is not so closely associated with just one G-protein, this gives it the potential for even more effects (see Greenhoff and Johnson 1997). 

Bogman, K., Peyer, A. K., Torok, M., Kusters, E., Drewe, J., HMG-CoA reductase inhibitors and P-glyco-protein modulation, Br. J. Pharmacol. 

Yoshikawa, H. Myelin-associated oligodendrocytic basic protein modulates the arrangement of radial growth of the axon and the radial component of myelin. Med. Electron Microsc. 34,160-164, 2001. 

Dolphin, A. C. G protein modulation of voltage-gated calcium channels. Pharmacol. Rev. 55 607-627, 2003. 

We doubt that there will prove to be a generally close linkage between DNA modules (exons) and protein modules (domains or sub-domains). In addition to the above arguments, the proposed linkage must also deal with the awkward problem that is posed by prokaryotic DNA, for which there is no evidence of introns. Nonetheless, we will continue to watch with great interest for additional relevant evidence. 

Lupas, a. N. and Koretke, K. K., Bioinformatic analysis of ClpS, a protein module involved in prokaryotic and eukaryotic protein degradation,... 

Mammalian HAT enzymes can be divided into subfamilies (Tan, 2001). However, it is currently difficult to classify a protein as a potential HAT enzyme based on its amino acid sequence, since these subfamilies display no obvious similarity in their primary sequence, nor in the size of their HAT domains or the surrounding protein modules (Kuo and Allis, 1998 Marmorstein, 2001). The only region that is partly conserved between HAT subfamilies, either on the amino acid sequence and/or structural level, is a small subdomain first noticed in GCN5-related N-acetyltransferases, which encompasses the coenzyme A (CoA) binding site (Neuwald and Landsman, 1997 Martinez-Balbas et al, 1998 Yan et al, 2000 Marmorstein and Roth, 2001). Four families of mammalian HATs that have been implicated in human disease will be discussed here. 

Brewster, N.K., Johnston, G.C., and Singer, R.A. (2001) A bipartite yeast SSRPl analog comprised of Pob3 and Nhp6 proteins modulates transcription. Mol. Cell. Biol. 21, 3491-3502. 

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