Nucleation proteins, function

SAMs of alkanethiolates on gold provide excellent model systems for studies on interfacial phenomena (e.g., wetting, adhesion, lubrication, corrosion, nucleation, protein adsorption, cell attachment, and sensing). These subjects have been reviewed previously [125,183-185]. Here we focus on applications that involve using chemical synthesis of functional SAMs after their assembly. 

In bone, collagens are the primary constituent in mollusk shell, silk-fibroins and polysaccharide fibrils are utilized The organization of these into a three dimensional, skeletal framewoik determines the form and function of the resulting hard tissue. Within the void spaces, nucleation proteins are deposited and the solution invading this network is brought to supersaturation with respect to the desired mineral phase. The nucleation proteins are thought to induce nucleation at the desired location. Qystal growth ensues and the void spaces are filled with mineral to form a fully dense ceramic/polymer composite. 

The microtubule-associated proteins MAP2 and tau both have two separate functional regions (Lewis et al., 1989). One is the microtubule-binding site, which nucleates microtubule assembly and controls the rate of elongation (by slowing the rate of assembly). The second functional domain shared by MAP2 and tau is a short C-terminal a-helical sequence that can cross-link microtubules into bundles by self-interaction. This domain has some of the properties of a leucine zipper. Likely it is responsible for the organization of microtubules into dense stable parallel arrays in axons and dendrites (Lewis et al., 1989). 

Rephcation errors, even with a very efficient repair system, lead to the accumulation of mutations. A human has 10 nucleated cells each with 3 X 10 base pairs of DNA. If about 10 cell divisions occur in a lifetime and 10 mutations per base pair per cell generation escape repair, there may evenmaUy be as many as one mutation per 10 bp in the genome. Formnately, most of these will probably occur in DNA that does not encode proteins or will not affect the function of encoded proteins and so are of no consequence. In addition, spontaneous and chemically induced damage to DNA must be repaired. 

It is not unreasonable to believe, for example, that the collision of two a-helices could become a nucleation site for protein folding. Thus, the alignment of two a-helical chains could determine the overall fold and, as a consequence, the function of the protein. 

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