Proteins machines

Ryan, K.J. and Wente, S.R. (2000) The nuclear pore complex a protein machine bridging the nucleus and cytoplasm. Curr. Opin. Cell Biol, 12, 361-371. 

Tagging individual proteins with fluorescent molecules allows them to be monitored in live cells, enabling rapid discovery of many intricate details about the cellular chemistry. For example, fluorescent tags on molecules that have been packaged into small vesicles have been monitored as they travel along microtubules within the axons via complex protein machines. 

Alberts B. The cell as a collection of protein machines preparing the next generation of molecular biologists. Cell 1998 92 291-294. 

A new protein, freshly made in the cell, encounters many molecular machines. Some of the machines grab hold of the protein and send it along to the location it is destined to reach. In a little while I will follow a protein along one pathway from start to finish. Protein machines all have rather exotic names, however, and it is difficult for many people to picture these things in their minds if they are not used to thinking about them. So I will first use an analogy, which will take the next several pages. 

The equivalent of induced fit vs. conformational selection for the case of a motor protein is power stroke (a force-generating conformational change driven by a chemical reaction) vs. diffusion and catch (thermal fluctuation, even against an external force, followed by stabilization by chemical reaction). As we have discussed above, the distinction is meaningful only kinetically. For protein machines, the energy involved is not much greater than the thermal energy, and hence one cannot expect that one of the two processes overwhelms the other. 

One common example of repetitive synthetic strategy comes from the field of natural products. The preparation of oligo- and polypeptides is a repeating sequence of protection and activation of the reactants, followed by the addition of a new amino acid. In 1963, one of the highlights in repetitive synthesis was the automation of peptide production by Merrifield8 (Figure 1). In the literature, authors often speak of a protein machine since it is now possible to build up peptides mechanically without the preparative help of a chemist. 

One criterion for a bona fide membrane-fusion protein is that membrane fusion can be reconstituted by transfection of the candidate fusion protein into nonfusing cells or by reconstitution into lipid vesicles (White, 1990 White, 1992 White and Blobel, 1989). Transfection of meltrin a into fibroblasts did not lead to an increase in cell fusion (Yagami-Hiromasa et al., 1995). Clearly, failure to reconstitute fusion does not rule out a role in fusion because the cellular fusion machinery may be more complex than viral fusion proteins. Muscle cells might contain other proteins that are required for meltrin a to promote membrane fusion but that are not expressed or active in fibroblasts. Ultimately, the identity of a bona fide cell-cell fusion protein or protein machine will only be determined by reconstituting membrane fusion with defined components. In the interim, it will be important to more accurately understand the roles of meltrin a and fertilin in the cascade of steps that result in membrane fusion and thereby perhaps distinguish between a direct and indirect role in fusion. 

Hardison, R. 1998. Hemoglobins from bacteria to man Evolution of different patterns of gene expression. J. Exp. Biol. 201 1099. Lesk, A. M. 2001. Introduction to Protein Architecture. Oxford. Macromolecular Machines. 1998. Ceil92 291-423. A special review issue on protein machines. 

Finally, the electron microscope will become the dominant instrument for studying protein machines in vitro and in situ. Tomographic methods applied to single cells and molecules combined with automated reconstruction methods will generate models of protein-based structures that cannot be determined by x-ray crystallography. High resolution three-dimensional models of molecules in cells will help explain the intricate biochemical interactions among proteins. 

Single entity Complexes of multiple entities (including protein machines)... 

The contractile protein machines of Life, however, accomplish more than the mechanical work of pumping iron or of rotation. 

Knowledge of how contractile protein machines can sustain Life provides the capacity to design protein-based materials. 

The reduced nicotinamides and ATP convert carbon dioxide (CO2) to carbohydrate, [C(H20)]6, by means of the protein machines of the dark reactions, known as the Calvin cycle. 

As seen above, the two primary molecular players of photosynthesis and respiration are nicotinamide and ATP. Both of these key molecules effect change in the charge of a protein machine during its function. In particular. 

Synthetic Model Protein Machines Emulate Energy Conversions of Photosynthesis, Respiration, and Motion... 

Synthetic Model Protein Machines Pump Protons on Reduction... 

Synthetic Elastic-contractile Model Protein Machines to Energize Phosphates... 

Progression to Biology s Machines from Model Protein Machines... 

Consequences of Protein Machines Based on the Inverse Temperature Transitions... 

The Essential Role of Protein Machines Within the Cell Membrane... 

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