Up-and-down helix bundles

A. Up-and-down helix bundles Myohemerythrin, hemerythrin Cytochrome b5(B Cytochrome c ... 

Protein A fragment, staphylococcal (Deisenhofer et ah, 1978) Up-and-down helix bundle (Fig. 72)... 

Domain 1 classic doubly wound (3 sheet Domain 2 up-and-down helix bundle Trypsin (Stroud et al., 1974)... 

Tobacco mosaic virus protein has a small, highly twisted antiparallel j8 sheet at the base of the helix bundle, with two more helices underneath the sheet (see Fig. 72). Cytochrome bs looks remarkably similar (see Fig. 105), but the helices are much shorter. That structure could have been classified as an up-and-down helix bundle, but we have placed it in the small metal-rich proteins because its helix bundle is very small and distorted and the heme interactions appear more important than the direct helix contacts. 

Fig. 87. Myohemerythrin as an example of an up-and-down helix bundle, (a) a-Carbon stereo (b) schematic drawing of the backbone structure, from the same viewpoint as in a.

Figure 89 illustrates two different tries at simplified representation of the globin structure. For reference, Fig. 89a shows the hemoglobin /3 chain in stereo. Figure 89b shows the globin structure schematically as two layers of helices with the elements in one layer approximately perpendicular to those in the other layer this can be contrasted with a possible description of the up-and-down helix bundles as two layers with their elements approximately parallel to each other. The perpendicular layers provide a rather successful simple schema for the globin structure, but unfortunately there are no other proteins that can be adequately described as two perpendicular layers of helices. Also, specification of the topology in this scheme is cumbersome, since the chain skips back and forth between layers. 

Figure 89c schematizes the globin structure as a twisted cylinder of helices, analogous to the antiparallel /8 barrels to be discussed in Section III,D. The up-and-down helix bundle structures are of course also readily described as cylinders, so that this schema makes the... 

Fig. 105. Examples of small disulfide-rich or metal-rich proteins (shown on the right side) compared with their more regular counterparts in other structural categories (shown at the left), (a) Tobacco mosaic virus protein, an up-and-down helix bundle (b) cytochrome bs, a distorted up-and-down helix bundle (c) trypsin domain 1, a Greek key antiparallel /3 barrel (d) high-potential iron protein, a distorted Greek key /3 barrel (e) glutathione reductase domain 3, an open-face sandwich fi sheet (f) ferredoxin, a distorted open-face sandwich f) sheet.

FIGURE 12.36. Various types of protein tertiary structure, (a) An antiparallel a structure (cytochrome 6502) an up-and-down helix bundle (Ref. 113), (b) an antiparallel / structure (Cu,Zn superoxide dismutase) a Greek key (3 barrel (Ref. 114), and (c) and a parallel aj structure (triose phosphate isomerase) a singly wound parallel 0 barrel (Ref. 115). (Courtesy Jane S. Richardson)... 

The most common type of an all-a motif is the simple up-and-down helix bundle with near neighbour connectivity (Figure 15.12). Four helices form a good stable structure most examples show straightforward up-down connectivity, although there are two examples of crossover connections between parallel helices, in porcine growth hormone and ferritin [37]. 

Either up-and-down or Greek key helix bundle Pyruvate kinase (Stuart et ah, 1979)... 

All but one of the above structures have four helices in the bundle, with + 1,+ 1,+ 1 connections. For the up and down topology on a cylinder, handedness can be defined by whether the chain turns to the right or to the left at the end of the first structure element (whether it is a helix or a /3 strand). With an even number of helices, reversing N to C direction of the chain also reverses handedness of the topology for an odd number of helices or strands handedness is invariant to chain reversal. For + 1, + 1, +1 topologies in general, handedness is not... 

The connectivity is not known for the seven-helix bundle of purple membrane protein (Henderson and Unwin, 1975), but on the basis of its resemblance to other antiparallel a proteins the most likely topologies would be either up-and-down or Greek key (see below). An analysis based on the sequence and the relative electron-densities of the helices (Engelman et ah, 1980) considers a left-handed up-and-down topology as the most probable model. 

The first type of anti parallel /3 barrel, in analogy with the first type of helix bundle, has simple up and down +1,+ 1,+ 1 connections all around. Although it is relatively unusual for a barrel to be composed entirely of up-and-down strands, many of the larger barrels and sheets have four- to six-stranded sections of simple up-and-down topology... 

Figure 2-22 Ribbon drawing of an up-and-down four-helix bundle in myohemerythrin. The two spheres represent the two iron atoms which carry an 02 molecule. They are coordinated by histidine and aspartate side chains. Courtesy of J. Richardson.117...

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. 

Figure 13.18 Ribbon diagram of the structure of human growth hormone. The fold is a four-helix bundle with up-up-down-down topology, and consequently there are two long cross-connections between helices A and B as well as between helices C and D. (Adapted from J. Wells et al., Annu. Rev. Biochem.

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,... 

The predominant feature of each o-helical cytokine structure is a left-handed anti-parallel four-helix bundle (Fig. 2) (Presnell and Cohen, 1989 Sprang and Bazan, 1993). The four helices of the bundle are connected by two long overhand connections and one short segment to form a distinct up-up-down-down topology first described for porcine growth hormone... 

Hi. Ml. Ml mediates encapsidation of nucleoprotein cores into the envelope and interacts with both RNA and the membrane. The structure of a fragment (residues 2—158 of 252) shows two 4-helix bundle domains (Sha and Luo, 1997). The N-terminal domain is a classic up—down bundle. The second is a variant in which diagonally opposite helices are connected, a crossed helix bundle, so that each helix has one neighbor that is parallel, one that is antiparallel. There is a presumed third domain of unknown structure. Hydrophobic residues on one surface of the N-terminal domain are buried at an interface to the second domain, but with a conformational change could become exposed to a membrane surface. Positively charged residues are on the surface of the second domain and could interact with RNA. 

Fold All a helix four-helix up-down bundle. There are additional short helices at the N and C termini. Structures for... 

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