Protein secondary barrels

The structural solution for the vast majority of OM proteins is provided in the form of the (3-strand, a secondary fold, which allows portions of the polypeptide chain to organise as a (3-barrel. In this cylindrical structure, hydro-phobic residues point outwards and hydrophilic residues are located inside, which can allow the formation of a water-filled channel [30 33]. 

Figure 17.31 shows a model of porin from the outer membrane of the bacterium Rhodobacter capsulatus. Unlike most integral membrane proteins, porins have a j8-stranded secondary structure. The R. capsulatus protein appears to form a 16-stranded /3 barrel that crosses the membrane as a tube. The tubular molecules aggregate as trimers with three parallel pores. 

Work by Stefan Matile in Geneva, Switzerland, has resulted in a number of interesting [i barrel mimetic anion transporting pores such as 12.38 (Figure 12.17).27 A [5 barrel is a kind of natural protein that forms a rigid channel by self-assembly of peptides into a /3-sheet type of secondary structure. The peptide backbone is mimicked by the rigid octaphenyl backbone which is ca. 3.4 nm long and hence spans... 

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). 

Certain combinations of secondary superstructures are often found in proteins and control their structure and function. The most frequent is the /fayS-unit, where an a-helix bridges two /1-strands. This is the prevailing feature in most coenzyme-binding domains of dehydrogenases [7]. Other important superstructures include a,a-dimers, /1-meanders and //-barrels. 

Fig. 12. a/fi barrel domain of MR (based on Protein Data Bank entry 1 mnr). Important active site residues and the associated secondary structure elements are labeled and designated with arrows. From Babbitt and Gerlt (1997, Figure 1, p. 30592). 

Rational protein engineering aims to exchange and fuse secondary structure elements and domains at precise locations, based on predictions through rational means, to form a functional hybrid structure. Despite the great complexity involved in rational protein engineering, two outstanding experimental successes were recently reported for /1-barrel and f>/a-barrel structures. 

The capsid is composed of 60 copies of three classic jelly-roU j3 barrels (VPl, VP2, and VPS), and a small VP4 on the inside surface of the capsid. The proteins vary in length, between about 230 and 300 amino acids. The corresponding proteins of different viruses are more similar to one another than are VP1-VP3 within one species (Rossmann, 1987). VPl and VPS have N-terminal extensions to the barrel that meander away to form contacts with neighboring subunits (Hogle et al, 1985 Rossmann et al, 1985). The VP2 extension forms an additional j3 ribbon on the RNA side of the capsid. Various secondary structural elements are inserted within the loops. Like SBMV, there is a helix in the CD loops of all of the capsid proteins of poliovirus, rhinovirus, and so on. In the picornavimses there is a short helix either breaking or preceding /3B. 

Supersecondary structure A pattern of protein structure that is not an entire domain but is at a higher level than secondary structure. Examples are yS barrels and Greek-key structures. 

Many globular proteins contain combinations of a-helix and /Tpleated sheet secondary structures (Figure 5.20). These patterns are called supersecondary structures. In the /la/1 unit, two parallel /Tpleated sheets are connected by an a-helix segment. In the fi-meander pattern, two antiparallel /1-sheets are connected by polar amino acids and glycines to effect an abrupt change in direction of the polypeptide chain called reverse or fi-turns. In aa-units, two successive a-helices separated by a loop or nonhelical segment become enmeshed because of compatible side chains. Several j8-barrel arrangements are formed when various... 

Normal mode analysis of the mechanical properties of a triosephosphate isomerase-barrel protein suggests that the region between the secondary structures plays an important role in the dynamics of the protein. The beta-barrel region at the core of the protein is found to be soft in contrast to the helical, strand and loop regions [62]. A detailed discussion of other properties of proteins is mechanically highly non-linear systems is given by Kharakoz [63]. 

Some membrane proteins span the hpid bilayer several times, with hydrophobic sequences of about 20 amino acid residues forming transmembrane a helices. Detection of such hydrophobic sequences in proteins can be used to predict their secondary structure and transmembrane disposition. Multistranded j3 barrels are also common in integral membrane proteins. Tyr and Trp residues of transmembrane proteins are commonly found at the lipid-water interface. 

Tertiary Structure - Attempts to predict tertiary structure of proteins have not been as successful as those for predicting secondary structure. Folding of sequences depends critically on specific side chain interactions, often far removed from one another in the amino acid sequence. Attempts to predict tertiary structure include efforts to recognize overall patterns in tertiary folding combined with the prediction of secondary structure. These efforts have led to the successful prediction of an ot//f-barrel structure for tryptophan synthase, which is in excellent agreement with the structure determined by x-ray diffraction. 

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