P domain structures

P Domain structures. The cores of these domains are built up by 4-10... 

This chaperone is involved in the folding of proteins with a molecular weight of 20 to 60 KDa and contributes to forming the proper structures of about 10 % to 15 % of all proteins expressed in a cell (Ewalt et al. 1997). Polypeptides with an a/p domain structure have been shown to preferably attach to this chaperone for folding. 

Domains are formed by different combinations of secondary structure elements and motifs. The a helices and p strands of the motifs are adjacent to each other in the three-dimensional structure and connected by loop regions. Sequentially adjacent motifs, or motifs that are formed from consecutive regions of the primary structure of a polypeptide chain, are usually close together in the three-dimensional structure (Figure 2.20). Thus to a first approximation a polypeptide chain can be considered as a sequential arrangement of these simple motifs. The number of such combinations found in proteins is limited, and some combinations seem to be structurally favored. Thus similar domain structures frequently occur in different proteins with different functions and with completely different amino acid sequences. 

On the basis of simple considerations of connected motifs, Michael Leviff and Cyrus Chothia of the MRC Laboratory of Molecular Biology derived a taxonomy of protein structures and have classified domain structures into three main groups a domains, p domains, and a/p domains. In ct structures the core is built up exclusively from a helices (see Figure 2.9) in p structures the core comprises antiparallel p sheets and are usually two P sheets packed... 

The most frequent of the domain structures are the alpha/beta (a/P) domains, which consist of a central parallel or mixed P sheet surrounded by a helices. All the glycolytic enzymes are a/p structures as are many other enzymes as well as proteins that bind and transport metabolites. In a/p domains, binding crevices are formed by loop regions. These regions do not contribute to the structural stability of the fold but participate in binding and catalytic action. 

Figure 4.7 Two of the enzymatic activities involved in the biosynthesis of tryptophan in E. coli, phosphoribosyl anthranilate (PRA) isomerase and indoleglycerol phosphate (IGP) synthase, are performed by two separate domains in the polypeptide chain of a bifunctional enzyme. Both these domains are a/p-barrel structures, oriented such that their active sites are on opposite sides of the molecule. The two catalytic reactions are therefore independent of each other. The diagram shows the IGP-synthase domain (residues 48-254) with dark colors and the PRA-isomerase domain with light colors. The a helices are sequentially labeled a-h in both barrel domains. Residue 255 (arrow) is the first residue of the second domain. (Adapted from J.P. Priestle et al., Proc.

Figure 4.21 The polypeptide chain of the arabinose-binding protein in E. coli contains two open twisted a/P domains of similar structure. A schematic diagram of one of these domains is shown in (a). The two domains are oriented such that the carboxy ends of the parallel P strands face each other on opposite sides of a crevice in which the sugar molecule binds, as illustrated in the topology diagram (b). [(a) Adapted from J. Richardson.)...

The a/p-barrel structure is one of the largest and most regular of all domain structures, comprising about 250 amino acids. It has so far been found in more than 20 different proteins, with completely different amino acid sequences and different functions. They are all enzymes that are modeled on this common scaffold of eight parallel p strands surrounded by eight a helices. They all have their active sites in very similar positions, at the bottom of a funnel-shaped pocket created by the loops that connect the carboxy end of the p strands with the amino end of the a helices. The specific enzymatic activity is, in each case, determined by the lengths and amino acid sequences of these loop regions which do not contribute to the stability of the fold. 

Antiparallel beta (P) structures comprise the second large group of protein domain structures. Functionally, this group is the most diverse it includes enzymes, transport proteins, antibodies, cell surface proteins, and virus coat proteins. The cores of these domains are built up by p strands that can vary in number from four or five to over ten. The P strands are arranged in a predominantly antiparallel fashion and usually in such a way that they form two P sheets that are joined together and packed against each other. 

Figure S.12 Schematic diagram of the path of the polypeptide chain In one domain (the blue region in Figure 5.11) of the y-crystallln molecule. The domain structure is built up from two P sheets of four antiparallel p strands sheet 1 from p strands 1, 2, 4, and 7 and sheet 2 from strands 3, 5, 6, and 8.

Jurnak, E, et al. Parallel p domains a new fold in protein structures. Curr. Opin. Struct. Biol. 4 802-806, 1994. 

Jeffrey, P.D., Gorina, S., Pavletich, N.P. Crystal structure of the tetramerization domain of the p53 tumor suppressor at 1.7 Angstroms. Science 267 1498-1502, 1995. 

Figure 11.7 Schematic diagram of the structure of chymotrypsin, which is folded into two antiparallel p domains. The six p strands of each domain are red, the side chains of the catalytic triad are dark blue, and the disulfide bridges that join the three polypeptide chains are marked in violet. Chain A (green, residues 1-13) is linked to chain B (blue, residues 16-146) by a disulfide bridge between Cys 1 and Cys 122. Chain B is in turn linked to chain C (yellow, residues 149-245) by a disulfide bridge between Cys 136 and Cys 201. Dotted lines indicate residues 14-15 and 147-148 in the inactive precursor, chmotrypsinogen. These residues are excised during the conversion of chymotrypsinogen to the active enzyme chymotrypsin.

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.

The overall structure of the variable domain is very similar to that of the constant domain, hut there are nine p strands instead of seven. The two additional p strands are inserted into the loop region that connects p strands C and D (red in Figure 15.8). Functionally, this part of the polypeptide chain is important since it contains the hypervariahle region CDR2. The two extra p strands, called C and C", provide the framework that positions CDR2 close to the other two hypervariahle regions in the domain structure (Figure 15.8). 

The molecular basis for quasi-equivalent packing was revealed by the very first structure determination to high resolution of a spherical virus, tomato bushy stunt virus. The structure of this T = 3 virus was determined to 2.9 A resolution in 1978 by Stephen Harrison and co-workers at Harvard University. The virus shell contains 180 chemically identical polypeptide chains, each of 386 amino acid residues. Each polypeptide chain folds into distinct modules an internal domain R that is disordered in the structure, a region (a) that connects R with the S domain that forms the viral shell, and, finally, a domain P that projects out from the surface. The S and P domains are joined by a hinge region (Figure 16.8). 

When they form the three subunits A, B, and C of the asymmetric unit, the identical polypeptides adopt different three-dimensional structures. The C subunit in particular is distinct from the A and B structures, its hinge region assuming a different conformation so that the S and P domains are... 

Morphology of the anionically synthesized triblock copolymers of polyfp-methyl-styrene) and PDMS and their derivatives obtained by the selective chlorination of the hard segments were investigated by TEM 146). Samples with low PDMS content (12%) showed spherical domains of PDMS in a poly(p-methylstyrene) matrix. Samples with nearly equimolar composition showed a continuous lamellar morphology. In both cases the domain structure was very fine, indicating sharp interfaces. Domain sizes were estimated to be of the order of 50-300 A. 

Figure 5-6. Examples of tertiary structure of proteins. Top The enzyme triose phosphate isomerase. Note the elegant and symmetrical arrangement of alternating p sheets and a helices. (Courtesy of J Richardson.) Bottom Two-domain structure of the subunit of a homodimeric enzyme, a bacterial class II HMG-CoA reductase. As indicated by the numbered residues, the single polypeptide begins in the large domain, enters the small domain, and ends in the large domain. (Courtesy ofC Lawrence, V Rod well, and C Stauffacher, Purdue University.)...

The human caliciviruses, norovirus (NoV) and sapovirus, have also been described as small round structured viruses, for their 27-30 nm capsids. The NoV capsid consists of 180 copies of the VPl major capsid protein packed as an icosahedron (Prasad et ah, 1999) and the VP2 minor capsid protein, which may contribute to stability (Bertolotti-Ciarlet et al., 2002). The S domain of VPl forms the inner shell of the capsid, while the P domain protrudes from the capsid surface and contributes to binding the histoblood group antigen receptor (Cao et ah, 2007) and antigenicity (Donaldson et ah, 2008 Lindesmith et ah, 2010). 

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