The Functional Domain

FIGURE 9.27 The O-Unked saccharides of glycoproteins appear in many cases to adopt extended conformations that serve to extend the functional domains of these proteins above the membrane surface. (Adaptedfrom Jentofi, N., 1990, Trends in Biochemical Sciences 15 291-294.)... 

In addition to this large movement of the Rieske protein, small but nevertheless significant conformational differences within the functional domain are observed. The structure of the functional domain of the Rieske subunit in the PGi22 crystal form showing the ci positional state is the same as that of the water soluble fragment... 

ISF). However, in the P6s crystal form ( intermediate state ), the cluster binding subdomain appears to be detached from the base fold fi sheets 1 and 2) in an open conformation 42). If the functional domains of the two crystal forms are superposed using the base fold residues, the rms deviation of the Ca positions of the cluster binding... 

In the family of cation pumps, only the Na,K-ATPase and H,K-ATPase possess a p subunit glycoprotein (Table II), while the Ca-ATPase and H-ATPase only consist of an a subunit with close to 1 000 amino acid residues. It is tempting to propose that the p subunit should be involved in binding and transport of potassium, but the functional domains related to catalysis in Na,K-ATPase seem to be contributed exclusively by the a subunit. The functional role of the P subunit is related to biosynthesis, intracellular transport and cell-cell contacts. The P subunit is required for assembly of the aj8 unit in the endoplasmic reticulum [20]. Association with a j8 subunit is required for maturation of the a subunit and for intracellular transport of the xP unit to the plasma membrane. In the jSl-subunit isoform, three disulphide... 

Chia We have looked at the potential phosphorylation sites of Insc, and this is the only apical complex component for which the functional domain has been defined. All the putative Cdc2 phosphorylation sites lie outside the region required for function (at least using an over-expression paradigm). For the other two known components, Baz and Pins, we don t know which the functional parts of the molecule are. It seems more appealing to think in terms of effects on the cytoskeleton, and in particular actin. 

Narayanaswami, V., Maiorano, J. N., Dhanasekaran, P. et al. Helix orientation of the functional domains in apolipoprotein e in discoidal high density lipoprotein particles. /. Biol. Chem. 279 14273-14279, 2004. 

All fungal prion proteins have a so-called prion domain and a functional domain. The prion domain is a region of the polypeptide chain that is necessary and sufficient for prion formation and maintenance (Fig. 1 Wickner et al., 2002). For Ure2p and Sup35p, the functional domain is responsible for the cellular activity of the normal form of the protein. 

In Ure2p and Sup35p, the prion domain is at the N-terminus and the functional domain is at the C-terminus. In Rnqlp and HET-s, these positions are reversed. 

The sizes of the prion domains vary from 70 amino acid residues (HET-s) to 250 amino acid residues (Rnqlp) (Fig. 1), but their borders are not precisely defined by functional criteria since these domains may be subjected to sizeable truncations while retaining their prionogenic properties (Edskes and Wickner, 2002 Ross et al., 2005). Nor are they precisely defined by the extent of N/Q-rich tracts since not all prion domains have them and the preponderance of these residues can vary within a given prion domain. Since the functional domains tend to have globular folds (Section II.B), an operational definition of a prion domain may be that it terminates with the last (or first) residue that is not part of the functional domain, although this definition is applicable only when that fold is known. 

Meza, J. E., et al.. Mapping the functional domains of BRCAl. Interaction of the ring finger domains of BRCAl and BARDl. / Biol Chem, 1999, 274(9), 5659-65. 

The aforementioned properties make profile and HMM methods well suited for domain-detection purposes [8]. A large number of homology domains have been identified by each method, including several of the functional domains discussed below. 

Fig. 7.5. Functional domains of protein kinase A. The functional domains of the catalytic (C) and regulatory (R) subunits of protein kinase A (bovine) are shown in a hnear configuration. M myristoylation.

Fig. 7.8. Functional domains of protein kinase C. The functional domains of protein kinase Ca and C8 are shown as a linear representation. The binding site for TPA lies in domain Cl. Domain C2 contains the Ca binding site. Protein kinase C8 lacks the C2 elements and thus regulation by Ca. According to Azzi et ah, (1992). Pseudosubstrate autoinhibitory sequence with pseudosubstrate character.

Fig. 7.13. Primary structure and oligomeric structure of CaM kinase II of type p. a) Linear representation of the functional domain of CaM kinase Up. b) The ohgomeric structure shown is proposed for an octamer of type P, based on electron microscopic investigations (Kanaseki et al., 1991). The iV-terminal catalytic domain is represented as a larger circle, the C-terminal ohgomerization domain by a smaller circle. CaM calmodulin.

Fig. 9.7. Domain structure of pl20-GAP. The functional domains of pl20-GAP are shown in linear form. PH pleckstrin homology domain SH Sarc homology domain A2 possibly Ca -dependent phospholipid binding motif 1,2,3, conserved sequences characteristic for GTPase-sti-mulating activity.

Fig. 9.10. Domain structure of Raf kinase. Linear representation of the functional domains of c-Rafl kinase. CR control region.

Melino, S., Rufini, S., Sette, M., Morero, R., Grottesi, A., Paci, M. et al. (1999) Zn2+ ions selectively induce antimicrobial salivary peptide Histatin-5 to fuse negatively charged vesicles. Identification and characterization of a zinc-binding motif present in the functional domain. Biochemistry, 38, 9626-9633. 

Hammell, R. L., and Hitchcock-DeGregori, S. E. (1996). Mapping the functional domains within the carboxyl terminus of alpha-tropomyosin encoded by the alternatively spliced ninth exon./. Biol. Chem. 271, 4236-4242. 

With the 1 structure known, the functional domains of the enzyme can be more readily defined. By comparison with the proteolytic site of other serine active site proteases, it should be possible to deduce binding and catalysis functions that are common to serine proteases where structural homology is high, and to pursue the discovery of unique functions where homology is low. The structure of the carbohydrate binding domain can be compared with other fucose... 

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