P barrel motif

One of the first off-lattice minimalist models was developed by Honeycutt and Thirumalai (HT) in 1990 to model a p-barrel motif. It models each amino acid as a single bead like those previously described, but it incorporates much more realistic energetic interactions by accounting for both nearest- and non-nearest-neighbor forces as well as for bond and torsion angles. The HT model includes three different types of residues hydrophobic (B), hydrophilic (L), and neutral (N). Consider the sequence for this 46-residue protein B9N3(LB)4N3B9N3(LB)4L. Its Hamiltonian is as follows. 

We saw in Chapter 2 that the Greek key motif provides a simple way to connect antiparallel p strands that are on opposite sides of a barrel structure. We will now look at how this motif is incorporated into some of the simple antiparallel P-barrel structures and show that an antiparallel P sheet of eight strands can be built up only by hairpin and/or Greek key motifs, if the connections do not cross between the two ends of the p sheet. 

The polypeptide chain is folded into two domains (Figure 11.7), each of which contains about 120 amino acids. The two domains are both of the antiparallel p-barrel type, each containing six p strands with the same topology (Figure 11.8). Even though the actual structure looks complicated, the topology is very simple, a Greek key motif (strands 1-4) followed by an antiparallel hairpin motif (strands 5 and 6). 

Figure 11.8 Topology diagrams of the domain structure of chymotrypsin. The chain is folded into a six-stranded antiparallel p barrel arranged as a Greek key motif followed by a hairpin motif.

POU regions bind to DNA by two tandemly oriented helix-turn-helix motifs Much remains to be learnt about the function of homeodomains in vivo Understanding tumorigenic mutations The monomeric p53 polypeptide chain is divided in three domains The oligomerization domain forms tetramers The DNA-binding domain of p53 is an antiparallel P barrel... 

Matile, S. (2001) En route to supramolecular functional plastidty synthetic P-barrels, the barrel-stave motif, and related approaches. Chemical Society Reviews, 30, 158-167. 

Figure 4.9 (a) Triose phosphate isomerase (TIM), has a (3-a-(3 structure made up of eight P-a motifs terminating in a final a-helix, which form a barrel-like structure, (b) An open twisted P-sheet with helices on both sides, such as the coenzyme-binding domain of many dehydrogenases. (From Branden and Tooze, 1991. Reproduced by permission of Garland Publishing, Inc.)... 

Fig. 5. Protein folding. The unfolded polypeptide chain collapses and assembles to form simple structural motifs such as p-sheets and a-helices by nucleation-condensation mechanisms involving the formation of hydrogen bonds and van der Waal s interactions. Small proteins (eg, chymotrypsin inhibitor 2) attain their final (tertiary) structure in this way. Larger proteins and multiple protein assemblies aggregate by recognition and docking of multiple domains (eg, p-barrels, a-helix bundles), often displaying positive cooperativity. Many noncovalent interactions, including hydrogen bonding, van der Waal s and electrostatic interactions, and the hydrophobic effect are exploited to create the final, compact protein assembly. Further structural...

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). 

P barrel The folding of a polypeptide chain to form a barrel-shaped structure with eight p strands as the lining. Eight a helices lie outside this p sheet. Both the a helices and the P strands follow a right-handed spiral around the axis of the barrel. The amino acid sequence in such a protein is such that p sheet and a helix alternate to give Pa)s- This motif was first seen in triose phosphate isomerase, and has since been observed in many other protein structures. 

Human ceruloplasmin consists of a single polypeptide chain with a MW of 132 kDa folded in six cupredoxin domains arranged in a triangular array. Each domain comprises a p-barrel, constructed in a Greek key motif, typical for the cupredoxins. Three of the six copper ions are bound to T1 sites present in domains 2, 4, and 6, whereas the other three copper ions form a trinuclear cluster, bound at the interface between domains 1 and 6 (Fig. 10). The spatial relation between the trinuclear center and the nearest T1 site (A, in domain 6) closely resembles that found in AO and was taken to further support the proposal that hCp has an oxidase function. The three T1 sites are separated from each other by a distance of 1.8 nm, a distance that might still allow for internal ET at reasonable rates and could also increase the probability for electron uptake. The coordination sphere of the T1 site in domain 4 (TIB) is identical with that of domain 6 (TIA). The third type 1 center (TIC), however. 

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