Translation protein targeting

One Holy Grail in protein structure is to develop tools that accurately predict three-dimensional structures of proteins from their primary sequence information [58, 59]. Many of the best tools to date only go part of the way by using known three-dimensional structures from proteins which share similar primary sequence to model the possible structures of new proteins. This technology still has a long way to go, but the potential rewards would be enormous, allowing a genome sequence to be translated into targets for therapeutic intervention in si-lico, in relatively short periods of time. 

Herbert, T. P., and Proud, C. G. (2006). Regulation of translation elongation and the cotranslational protein targeting pathway. In Translational Control in Biology and Medicine (M. B. Mathews, N. Sonenberg, andj. W. B. Hershey, eds.), pp. 601-624. Cold Spring Harbor Laboratory Press, Cold Spring, NY. 

One of the most important considerations for the improvement of protein yields is subcellular protein targeting, because the compartment in which a recombinant protein accumulates strongly influences the interrelated processes of folding, assembly and post-translational modification. All of these contribute to protein stability and hence help to determine the final yield [88]. 

Cox, J.C., Hayhurst, A., Hesselberth, J., Bayer, T.S., Georgiou, G., and Ellington, A.D., Automated selection of aptamers against protein targets translated in vitro from gene to aptamer. Nucleic Acid Res., 30(20), 1-14, 2002. 

In contrast to ubiquitin, the covalent attachment of ubiquitin-like molecules (Ubls) to other proteins seems to be more important for post-translational protein modification than for protein degradation. There is not much known yet about the subcellular distribution of these proteins but since they are frequendy involved in targeting functions it can be assumed that they are also subjected to a spatial organization. 

Translation in prokaryotes (H2) Translation in eukaryotes (H3) Protein targeting (H4)... 

Figure 10.8. Gene identification by Procrustes. The nucleotide sequence encoding human lysozyme is used as a query sequence to identify its gene structure against known protein sequence (i.e., pig lysozyme protein). The output includes sequence aignment of the source (predicted translate) versus target protein (pig lysozyme).

The conversion of nucleic acid into protein information doesn t completely solve the problem of translation. Proteins must be targeted to their appropriate locations, either inside or outside the cell. In eukaryotes especially, proteins must be broken down at appropriate rates some proteins have longer half-lives than others do. These steps are all possible points for cellular control. 

Protein antibodies, peptides, protein domains, functional proteins, clarified cell lysates enzymatic assays, mapping protein-DNA interactions, mapping protein-protein interactions, mapping post-translational modifications, target deconvolution, antibody, binding screens, protein expression profiling and biomarker discovery 13, 17, 23, 33-35, 37, 38, 41, 42, 45, 47, 66-75... 

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