Three-dimensional self-assembly proteins

VI. PREDESIGNED THREE-DIMENSIONAL SELF-ASSEMBLY OF PROTEINS CRYSTAL ENGINEERING ... 

The information difference that exists between the linear order of polypeptides and the three-dimensional order of proteins can be illustrated with a simple example. The linear order of 100 punctiform amino acids is specified by 100 coordinates, while their three-dimensional organisation requires 300 coordinates (three for each amino acid). Protein folding, or self-assembly, amounts therefore to adding the 200 missing coordinates to the 100 coordinates provided by the genes. And since the complexity of a system is determined by the number of parameters that are required to describe it, it is clear that protein folding is a phenomenon that produces an increase of complexity. 

Development of methodologies for protein self-assembly into a predesigned three-dimensional protein lattice carries potential for the construction of protein scaffolds, offering potential applications such as platforms for the ordered positioning of other proteins via protein fusion or of organic molecules by specific binding. 

Nanostructures are, literally, facts of life in biology. Proteins, viruses, and bacteria are nanosized, three-dimensional structures which have been self assembled from smaller subunits. Although individual atoms in the subunits (polypeptides, for example) are covalently linked, assembly of the subunits is maintained by non-covalent (van der Waals, hydrogen-bonding, electrostatic, and hydrophobic) interactions. 

The functional properties of proteins, like those of other biomolecules, are determined by their three-dimensional structures. Proteins possess an extremely important property a protein spontaneously folds into a welldefined and elaborate three-dimensional structure that is dictated entirely by the sequence of amino acids along its chain (Figure 1.6). The self-folding nature ofproteins constitutes the transition from the one-dimensional world of sequence information to the three-dimensional world of biological function. This marvelous ability of proteins to self assemble into complex... 

The hydrophobic effect is a driving force in the formation of clathrate hydrates and the self-assembly of lipid bilayers. Hydrophobic interactions between lipids and proteins are the most important determinants of biological membrane structure. The three-dimensional folding pattern of proteins is also determined by hydrophobic interactions between nonpolar side chains of amino acid residues. 

Biological systems provide numerous examples of self-assembled objects. Owing to the relatively weak interactions involved, a self-assembled structure is much more sensitive and responsive to its environment than a more rigid structure held together by covalent bonds. Unlike processes involving simple surfactants, polymers, and nanoparticles, self-assembly processes in biological systems are usually directional and functional and often lead to the formation of extremely complex structures. For example, the three-dimensional structure adopted by a protein in solution is critical to the protein s function, and this structure is determined by both strong (covalent) and weak... 

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