G protein functions

The SWISS-PROT database [36] release 40.44 (February, 2003) contains over 120 000 sequences of proteins with more than 44 million amino adds abstracted from about 100 000 references. Besides sequence data, bibHographical references, and taxonomy data, there are highly valuable annotations of information (e.g., protein function), a minimal level of redundancy, and a high level of integration with other databases (EMBL, PDB, PIR, etc.). The database was initiated in 1987 by a partnership between the Department of Medicinal Biochemistry of the University of Geneva, Switzerland, and the EMBL. Now SWISS-PROT is driven as a joint project of the EMBL and the Swiss Institute of Bioinformatics (SIB). 

Abnormal G protein functioning dysregulates adenylate cyclase activity, phosphoinositide responses, sodiurrypotassiunVcalcium channel exchange, and activity of phospholipases. Abnormal cyclic adenosine monophosphate and phosphoinositide secondary messenger system activity. 

The identification of the fold is, however, only a minor part of protein characterization. Function is a loosely defined term, but must be viewed within a particular context, e.g., protein function can only take place with an interaction partner or within cellular cascades and networks. Fold predictions and homology searches can only give partial answers to such higher order functions. Thus, independent functional features have to be collected and put into context. Such features include not only molecular properties, but also cellular roles, expression patterns, dysfunctions, pathway context, and subcellular localization. The latter can be predicted by exploiting a variety of methods and localization sites. Kenta Nakai reviews many such sites and their implementation... 

ME BACTERIAL TOXINS INTERFERE WITH G PROTEIN FUNCTION... 

Avissar S, Nechamkin Y, Roitman G, et al. Reduced G-protein functions and immunoreactive levels in mononuclear leukocytes of patients with depression. Am J Psychiatry 1997 154 211-217. 

Will-Shahab, L., Rosenthal, W., Schulze, W., and Kuttner, I. 1991. G protein function in the ischaemic myocardium. Eur. Heart J. 12 135-138. 

Diacylglycerol was mentioned as an activator of protein kinase C. In addition to diacylglycerol, protein kinase C is also activated by increased cellular calcium levels. Protein kinase C catalyzes, for example, the phosphorylation of G protein components the j8 subunit of the fiy complex and the a-GDP complex. Such phosphorylation apparently prevents the reassociation of the a-GDP with the fiy complex to give the G -GDP protein. It is thus clear that phosphorylation via protein kinase C participates in the regulation of G protein function. 

Ras G-proteins function as signalling switches, with on and off states. In the off state they are hound to the nucleotide GDP, while in the on state they are hound to GTP. In the GTP-bound conformation, ras has high affinity for numerous effectors, which allow it to carry out its functions. 

K. Bliiml. W. Schnepp, S. Schroder, M. Beyermann, M. Macias, H. Oschkinat, and M.J. Lohse. A small region in phosducin inhibits G protein function. EMBOJ, 16 (16), 4908-4915, 1997. 

Rasenick, M. M., Watanabe, M., Lazarevic, M. B., Hatta, S., Hamm, H. E. Synthetic peptides as probes for G-protein function - Carboxyl terminal Gas peptides mimic Gs and evoke high-affinity agonist binding to p-adrenergic receptors. J. Biol. Chem., 1994, 269, 21519-21525. 

Fig. 3.7 Schematic Presentation of G-Protein Functions in Signal Transduction 3. Transporters (Translocators) ...

Figure 8-3. The production and action of cyclic AMP (cAMP). G = G protein. G proteins function when GTP is bound 0 = free catalytic subunits l ] = regulatory subunits of protein kinase A ffi = stimulates.

Operationally, the heterotrimeric G-proteins function by means of a well defined catalytic cycle (Fig. 1). In this, the de-binding of GDP followed by the subsequent binding... 

Kalinowski RR, Jaffe LA, Foltz KR, Giusti AF. 2003. A receptor linked to a Gi-family G-protein functions in initiating oocyte maturation in starfish but not frogs. Dev Biol 253(1) 139-149. 

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