Four-helix bundle structures classes

Like other hormones in this class of cytokines, GH has a four-helix bundle structure as described in Chapter 3 (see Figures 3.7 and 13.18). Two of the a helices, A and D, are long (around 30 residues) and the other two are about 10 residues shorter. Similar to other four-helix bundle structures, the internal core of the bundle is made up almost exclusively of hydrophobic residues. The topology of the bundle is up-up-down-down with two cross-over connections from one end of the bundle to the other, linking helix A with B and helix C with D (see Figure 13.18). Two short additional helices are in the first cross-over connection and a further one in the loop connecting helices C and D. 

The overall three-dimensional structure of a protein is called the tertiary structure. The tertiary structure represents the spatial packing of secondary structures (Ofran and Rost, 2005). As for secondary structures, there are several different classes of tertiary structures. More advanced classification schemes take into account common topologies, motifs, or folds (Wishart, 2005). Common tertiary folds include the a/p-barrel, the four-helix bundle, and the Greek key (we will discuss protein folding further in Chapter 14). Any change to any part of the structure of a protein will have an impact on its biological activity (Thomas, 2003). 

The defining structural feature of the hematopoietic class of cytokines is a four-helix bundle motif organized into four anti-parallel hehces that adopt an up-up-down-down motif (Bazan, 1990a Sprang and Bazan,... 

A structural module comprising tetra(carboxylato)di-iron(II) centers with two additional A-donor groups has been identified at the active sites of the hydroxylase component (MMOH) of soluble methane monooxygenase, the R2 subunit of class I ribonucleotide reductase (RNR-R2), " " and stearoyl-acyl carrier protein (AGP) A desaturase (A9D). d8 structural comparisons of these enzymes reveal striking architectural similarities involving an approximately 18 A segment of a pseudo-222-symmetric four-helix bundle that encapsulates their di-iron active... 

Four helix bundles are a common structural motif that can be observed independently as well as components of large folding units. The six classes of four helix bundles constructed from four overlapping sets of helix pairs (where the helical axials are +20°... 

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