Proteins, /1-tums

Some of the procaryotic DNA-binding proteins are activated by the binding of an allosteric effector molecule. This event changes the conformation of the dimeric protein, causing the helix-tum-helix motifs to move so that they are 34 A apart and able to bind to the major groove. The dimeric repressor for purine biosynthesis, PurR, induces a sharp bend in DNA upon binding caused by insertion of a helices in the minor groove between the two... 

Harrison, S.C., Aggarwal, A.K. DNA recognition by proteins with the helix-tum-helix motif. Anna. Rev. Biochem. 59 933-969, 1990. 

While RNA molecules do not have the double stranded structure usually found in DNA, in many RNA molecules stem-loop structures are found in which the anti-parallel strands are connected by a 5-7 residue loop. Rather like the P-tum in proteins, this allows the... 

Fig. 16. An unusual interrupted helix from subtilisin (residues 62-86), in which the helical hydrogen bonds continue to a final tum that is formed by a separate piece of main chain. Such interrupted helices (broken on one side of the double helix) are apparently a fundamental feature of nucleic acid structure as illustrated by tRNA, but are exceedingly rare in protein structure.

Figure 2. Three-dimensional structure of human cytochrome c created by Protein Adviser, ver 3.0 (FQS, Hakata, Japan) with PDB file of human cytochrome c down-loaded from protein structure database of NCBI. a-Helices are shown as purple ribbons, random coils as white strands, and P-tums are blue (see separate colour tip). Heme c is depicted in white straight lines inside the protein.

The protein is a very compact molecule with a secondary structure having > 20 B-tums. 

Table 7.1 Conformational parameters for rif-helical, -sheet and F -turn residues in 29 proteins. The P, P and P are the conformational parameters for the different secondary stmctures, the fi s are the frequencies for occurrence of a given residue in the fe-tum. (Adapted from Prevelige and Fasman, 1989).

McGregor, M.J., Flores, T.P. and Sternberg, M.J.E. (1989) Prediction of -tums in proteins using a neural network. Protein Engineering, 2, 521-526. 

In 1975, Carswell et al. discovered that this bacterial-induced tumor killing activity could he transferred from one animal to another. When the serum of a mouse that is pretreated with LPS (also called endotoxin) is injected into another animal that has not been treated with endotoxin but harbors a transplantable skin tumor, the tumor undergoes necrosis. In addition, Carswell etal. also showed that addition of this substance (which they dubbed tum<.)r necrosis factor, or TNF) to cultures of transformed cells results in death of the cells (Helson ec al., 1975). It is now known that TNF is a member of a class of proteins called cytokines, which are immune hormones, that is, proteins that are secreted by certain immune cells during stimulation. These proteins are extraordinarily important in the immune response, by acting as the messengers between different cells to relay information (Abbas, 1991). 

Several DNA-binding motifs have been described, but here we focus on two that play prominent roles in the binding of DNA by regulatory proteins the helix-tum-helix and the zinc finger. We also consider a type of DNA-binding domain—the homeodomain—found in some eukaryotic proteins. 

Table 6. Frequency of (3-turn residues in 15 proteins, and, comparison of p-tum conformational parameters P, for 20 amino acids with their P and values105)...

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