P Propeller

Gq-GDP binds to the Gpy dimer through its GTPase domain in a region of the p propeller opposite to where G is bound (Figure 13.15). There are, therefore, no contacts between Gq and Gy in the heterotrimeric G py complex. The... 

In the complex with Gpy the two phosducin domains do not interact with each other, instead they wrap around the edge and the top side of the p propeller, to form an extensive interaction surface (Figure 13.17). The N-terminal domain of phosducin interacts with all of the top loops of the p propeller including part of the surface of Cpythat interacts with Gq (Figures 13.15 and 13.17). This interface between phosducin s N-terminal domain and Gpy clearly precludes association of the latter with Gq. 

The structure of the C-domain of hemopexin was determined first (128). The structure is a four-hladed p-propeller (Fig. 7), the smallest P-propeller known, and serves as the paradigm for the several proteins known to have a pexin domain, including vitronectin (108), and several metalloproteinases (107). The repeats evident in the sequence of hemopexin (99-101), for instance DAAV/F motifs and WD repeat, form a large part of the p-strands of the four blades, which are connected by short loops and a-helices. 

Fig. 7. The crystal structure of the C-domain of hemopexin (PDB accession number IHXN) 128) showed a four-bladed p-propeller structure, which because of sequence similarity was also expected in the N-domain. The high degree of beta structure and limited a-helix content agrees with the earlier FTIR analysis.

Fig. 5.4 A ribbon model of the G p-subunit, which has WD (Tip-Asp) repeats and forms p-propellers. This structure is like a scaffold, presenting a surface to which other proteins can bind. (The structure was solved in Paul Sigler s laboratory s and is reproduced with permission of the authors and Nature.)...

Cytochrome cd (nitrite reductase) is the only other protein, whose structure has been determined, that has an eight bladed p-propeller... 

Based on biochemical data (Aharoni et al, 2004 Josse et al, 1999a, b, c, 2001) but mainly on their 2.2 A-resolution crystal stmcture of a recombinant PONl variant (Hard et al, 2004), Tawfik and co-workers recently offered a model for the architecture and fimction of the lactonase active site(s) of the PON enzymes (Khersonsky and Tawfik, 2006 Rosenblat et al, 2006). According to the crystal stracture (Hard et al, 2004), PON is a six-bladed P-propeller, with two calcium ions located in the central tunnel - the structural Ca is buried while the catalytic Ca was solvent exposed. Two His residues, the so-called His -His " dyad, mediate the lactonase (and esterase) activity of PON enzymes the former acts as general base to activate a water molecule attacking the carbonyl oxygen of... 

Fig. 3 Glanzmann thrombasthenia mutations within the P-propeller stiucture of GPIIb A schematic drawing of the GPIIb p-propeller structural model showing the P-strands (arrows) and connecting strand arrangements . The propeller is drawn like a cylinder and each blade of the propeller is labeled W1-W7. The P-strands are numbered 1-4 with the first strand located toward the center and bottom and the fourth strand located outside and top of the cylinder. Hie wide ribbons represent the connections between the fourth P-strand of one blade and the first p-strand of the next blade. The ladder-like connections represent the calcium-binding domains and are located on the bottom of the cylinder. The Glanzmann thrombasthenia mutations are represented by black dots and the black bar in W2 represents an intradisulfide bond.

Fig. 4. Glazmann thrombasdienia mutations within the P-propeller sequence for GPIIb The amino-terminal sequence of GPIIb from residues 1-452 that form the seven blades of the p-propeller. The Glanzmann thrombosthenia mutations are shown under the GPIIb sequence and are listed by the patient designations as represented in Table 1. W1-W7 refer to the seven blades and the bold letters designate the amino acids that form the P-strands. The dashed line above the sequence in the second and third P-strand sequence of W2 designates the disulfide bond formed by the two cysteine residues affected by the Arab and patient CW deletion mutations and the italic letter that are underlined by dashes in W4-W7 represent the calcium-binding domains. ...

The book is divided into four major sections. It provides in the first part an introduction into two superfamilies of proteins with p-propellers, the WD40- and the Kelch-family. Lynn Cooley and Andrew M. Hudson provide evidence that the WD40- and Kelch-repeat families most likely did... 

Figure 2. Domain organisation, three-dimensional structure and sequence-into-colour translation of human coronin-lC. Top, True to scale schematic of the domain structure of human coronin-lC N, N-terminal coronin-specific signature, PI-7, p-propeller blades, C, unique C-terminal region, CC, coiled coll. Middle, top and side view of the structural homology model of human coronin-1 C, based on the crystal structure of human coronin-IA. p-propeller blades 1 and 2 that represent an unconventional and a typical p-propeller blade, respectively, are oriented to the bottom (left) and to the front (right). See also Chapter 5 by Bernadette McArdle and Andreas Hofmann. Figure 2 legend continued on the next page.

The P propeller domain is a widespread protein organizational motif. Typically, p-propeller proteins are encoded by repeated sequences where each repeat unit corresponds to a twisted P-sheet structural motif these P-sheets are arranged in a circle around a central axis to generate the p-propeller structure. Two superfamilies of P-propeller proteins, the WD-repeat and Kelch-repeat families, exhibit similarities not only in struaure, but, remarkably, also in the types of molectdar functions they perform. Whde it is unlikely that WL) and Kelch repeats evolved from a common ancestor, their evolution into diverse families of similar function may reflect the evolutionary advantages of the stable core P-propeller fold. In this chapter, we examine the relationships between these two widespread protein families, emphasizing recently published work relating to the structure and funrtion of both Kelch and WD-repeat proteins. 

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