Folding topology

Fig. 3. An example of fold topologies predicted from the maximization of secondary structure and the minimization of solvent-exposed hydrophobic residues. On the right is the basic three-dimensional packing of the secondary structure elements. Although no restrictions on the connectivity between these elements is shown, maximization of the secondary structure does imply some restrictions, such as those observed in most four-helix bundles and in all a/fi eight barrels. The top view on the right displays, as shaded, the buried hydrophobic sides of the amphipathic a helices and fi sheets.

Fig. 7. (a) Ribbon drawing of immunoglobulin domain, (b and c) Schematic of the folding topology of the immunoglobulin domain. 

The protein folds into two domains, each of which possesses the Greek key /3-sheet folding topology (see Figs. 14 and 15). The amino-terminal domain binds a type I copper, while the carboxy-terminal domain does not bind a type I copper. A second metal site is found between domain 1 of one molecule in the trimer and domain 2 of a second molecule, so that, in all, six metals are bound by the trimer. The second metal is bound by two histidines from domain 1 and one histidine from domain 2. Density for a fourth ligand suggests a hydroxyl or water as that ligand. 

Chart 10.2 Different folding topologies in the first-generation UPy modular polymer. 

PH domains bind phosphatidyl inositol derivatives and, due to this property, are able to mediate membrane association of signal proteins. The PH domain of PL-C61 binds to phospholipids such as Ptd(Ins)P2 with high affinity and specificity. The crystal structure of the PH domain of PL-C81 with bound Ptd(Ins)P2 surprisingly has a very similar folding topology to the PTB domain that specifically binds phosphotyrosine-containing peptides (see 8.2.3 review Lemmon et al, 1996). The importance of this similarity is not understood. 

Fig. 13.8. Structure of the inactive form of CDK2 in humans. The crystal structure of the human CDK2 apoenzyme shows a very similar folding topology to protein kinase A and other protein kinases (see Chapter 7). The occurrence of the aL12 element is specific for CDK2 this interferes with binding of ATP and substrate in the active form.

Structures of the catalytic core of HIV-1 integrase, HIV-l RNase H, RuvC, and the core domain of MuA transposase demonstrating similarities in folding topology. The catalytically essential residues... 

The (3 subunit contains two structural domains that correspond approximately to the N-and C-terminal halves of the polypeptide chain (Fig. 7.5 and color plates and ).7 Since the central core regions of these two domains have very similar folding topologies and are... 

Fig. 7.5 Folding patterns of the two domains of the / subunit. The core regions of these two domains (shown by diagonal stripes) have very similar folding topologies and are nearly superimposable. The pyridoxal phosphate Lys-87 Schiff base complex, shown in a ball-and-stick model, lies on the surface of each domain. P points to a region that contains several sites that are susceptible to proteolysis in the separate / subunit (see text). The cleavage sites (Lys-272, Arg-275, Lys-283, and Glu-296) are within a stretch of residues (260-310) that contains three long / hairpin loops and apparently lacks any other well-defined secondary structure (modified from Ref. 7). (See also color plates and .)...

X-ray crystallographic studies revealed that the ephrin RBD has a globular /3-barrel structure (Fig. 2B) with a Greek key folding topology... 

III. Folding Topology OF THE BCB Domains and Spectroscopic and Structural Properties of the Blue Copper Sites... 

Crystal structures of three phytocyanins are currently available. Two are for plantacyanins, from cucumber (also known as cucumber basic protein) (Guss et al., 1988, 1996) and from spinach (Einsle et al., 2000), and one is for the recombinant BCB domain of cucumber stella-cyanin (Hart et al., 1996). The three proteins display folding topology identical to one another, suggesting that phytocyanins fold into a uniform structure, which can be designated as a phytocyanin fold. As a historical note, the crystallization of the cucumber basic protein and its preliminary crystallographic data were reported in 1977, before any structure of a blue copper protein was available (Colman et al., 1977). However, the structure was solved in 1988 only by application of the then newly... 

Stellacyanin is also an important example of a heavily glycosylated protein for which the structure has been determined without its glyco components. It demonstrated that the carbohydrate moieties have virtually no effect on the folding topology of the polypeptide core of this particular glycoprotein. One of the three glycosylation sites in... 

Moore et al, 1991). The secondary structure of FKBP is about 35% /3 sheet and less than 10% helix. FKBP has an unprecedented antiparallel /3-sheet folding topology that results in the crossing of the two loops that connect strands of the sheet. This structural motif creates a hydrophobic cavity that is lined by a conserved array of six of the nine aromatic amino acids of the proteins. This cavity is the binding site for FK506 and probably is the isomerase active site. 

The two core proteins also have similar three-dimensional structures. Each core protein consists of two structural domains of about equal size and almost identical folding topology, which are related by approximately twofold rotation symmetry (Xia et al., 1997). Both domains are folded into one mixed 3 sheet of six or five p strands, flanked by three a helices from the other domain on the other side. Rotation of the C-terminal domain onto the N-terminal domain superimposes 134 a carbon from each domain of core 1 with r.m.s. deviation of 2.0, and 124 a carbons from each domain of core 2 with an r.m.s. deviation of 2.1. The overall shape of each core protein resembles a bowl, while the two core proteins enclose a big cavity that was also observed by electron microscopy (Akiba et al., 1996 Leonard et al., 1981). The amino acid residues lining the wall of the cavity are mostly hydrophobic. A small peptide, subunit 9 is found inside the cavity, mainly bound to core 2 protein (Figure 10). The bovine subunit 9 is an extended... 

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