P domain

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 4.13 (a) The active site in open twisted a/p domains is in a crevice outside the carboxy ends of the P strands. This crevice is formed by two adjacent loop regions that connect the two strands with a helices on opposite sides of the P sheet. This is illustrated by the curled fingers of two hands (b), where the top halves of the fingers represent loop regions and the bottom halves represent the P strands. The rod represents a bound molecule in the binding... 

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.)...

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

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 14.13 Stmcture of G-actin. Two a/P-domains, (red and green) bind an ATP molecuie between them. Tbis ATP is hydrolyzed when the actin monomer polymerizes to F-actin.

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... 

The S domains form the viral shell by tight interactions in a manner predicted by the Caspar and Klug theory and shown in Figure 16.8. The P domains interact pairwise across the twofold axes and form protrusions on the surface. There are 30 twofold axes with icosahedral symmetry that relate the P domains of C subunits (green) and in addition 60 pseudotwofold axes relating the A (red) and B (blue) subunits (Figure 16.9). By this arrangement the 180 P domains form 90 dimeric protrusions. 

Figure 16.9 Contacts between P domains in tomato bushy stunt virus. Sa, Sb, and Sc are the shell domains of subunits A, B, and C, respectively. Pa, Pb, and Pc are the protruding domains of subunits A, B, and C, respectively.

Goldstein SA, Bockenhauer D, O Kelly I et al (2001) Potassium leak channels and the KCNK family of two-P-domain subunits. Nat Rev Neurosci 2 175-184... 

The a- and P-domains have been isolated in order to study their role in the two reaction phases. The slow reactions occur predominately with the P-domain while the fast reaction is associated entirely with the a-domain [106]. This pattern follows other circumstances where the a-domain is more reactive than the P-domain. However, the P Site has Cd ions that are thermodynamically less tightly bound and more labile to inter-site exchange. 

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). 

Fig. 93. Topology diagrams for the doubly wound and miscellaneous a/p domains illustrated in Figs. 76 through 78. Arrows represent the P strands thin connections lie behind the p sheet and fat ones above it. The darkest upper box surrounds the classic doubly wound sheets successively lighter solid boxes include domains that are progressively less like the classic topology the dotted box encloses the miscellaneous a/P structures. K = kinase P = phospho DH = dehydrogenase ATCase = aspartate transcarbamylase.

Group I intron phosphotransesterification reactions are carried out by a conserved active site that contains a set of imperfect double helices named PI through P9. (See Figure 6.4.) P1-P9 helices are organized into three domains P1-P2, P4-P6, and P3-P9. Specifically, the Tetrahymena thermophila intron contains two sets of coaxially stacked helices that overlap to create the active site. These helices reside in two domains of approximately equal size P4-P6 and P3-P9. P domains are defined as base-paired regions, whereas J domains... 

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