Propeller Domain

The N-terminal region of the integrin a-subunit contains seven repeats of about 60 amino acids, which fold into a seven-bladed yS-propeller domain (Springer, 1997 Xiong et al, 2001) (Fig. 2A). A yS-propeller domain with the same topology is also found in the trimeric G-protein yS-subunit. The 

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Fig. 2. Examples of the structures of protein domains and repeats. The images were generated using Molscript (Kraulis, 1991). (A) Immunoglobulin domain (PDB identifier ltlk) (Holden et al1992), (B) A zinc finger domain with coordinated zinc ion (PDB identifienlzaa) (Pavletich and Pabo, 1991). (C) A /3-propeller domain composed of seven WD40 repeats (PDB identifier lgp2) (Wall et al., 1995), (D) An elongated domain of variant leucine-rich repeats (PDB identifienllrv) (Peters et al., 1996).

Fulop, V., Bocskei, Z., and Polgar, L. Prolyl Oligopeptidase An Unusual -Propeller Domain Regulates Proteolysis. Cell 1998, 94, 161-170. 

Springer, T. A. (1997). Folding of the N-terminal, ligand-binding region of integrin a-subunits into a /1-propeller domain. Proc. Natl. Acad. Sd. USA 94, 65-72. 

Fig. 3. Architecture of the kelch domain, (a) Stereoview of Domain II with the active site metal ion and protein ligands superimposed on a ribbon diagram of the polypeptide chain, (b) The modular organization of the sevenfold propeller domain is based on four-stranded antiparallel beta sheet subdomains.

Figure 20 The N-terminal /3-propeller domain of a-chain in integrin a3/3v (1JV2) contains seven repeated blades. Each blade (shown in one color) comprises four aligned /3-strands. Four calciiun ions boimd in this domain are located at blades 4-7...

Figure 26.20. Structure of Propeller Domaiu. The six-bladed propeller domain and an adjacent EGF-like domain of the LDL receptor.

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. 

Table 2. -propeller domain organization in representative proteins... 

While there is no structural information on coronin constructs that only contain the N-terminal WD repeat (propeller) domain, severe a tion has been reported for coronin 1 (lA) truncation mutants lacking the C-terminal extension and the coiled coil domain. The crystal structure of coronin 1 (1A) implies an eminendy important role of the C-terminal extension domain for the stability of the protein, especially for the residues direedy interactii with the p propeller. Appleton et aL have thus put forward the hypothesis that the region 1-392 of coronin 1 (lA), which comprises the WD repeat domain and the C-terminal extension, represents a folding unit, albeit this awaits experimental validation. Notably, a construct of coronin 3 (1C) extending from the last blade of the p propeller to the coiled coil domain (300-474), possesses secondary structure as predicted and thus appears to be folded. It still remains a matter of speculation, whether blade 7 adopts its native conformation within this construct because strand D is missing. 

A different situation has been found with coronin 3 (1C), where the deletion of the coiled coil domain abohshes plasma membrane binding. Taking into account the role of the coiled cod domain for homo-ohgomerisation and the fact that phosphorylation in this domain can alter the ohgomerisation state, a further twist becomes apparent. Phosphorylation of coronin 3 (1C) leads to a cytosolic relocation of coronin 3 (1C), i.e., loss of association with the plasma membrane. One could conclude that the membrane association of coronin 3 (1C) is also mediated by the P propeller domain, but that this only occurs with the trimeric species. In the absence of experimental data, other binding sites in the C-terminal domain of coronin 3 (1C) cannot be excluded, though. 

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