Folding domain

The Sema domain consisting of about 500 amino acids is characterized by highly conserved cysteine residues that form intramolecular disulfide bonds. Crystal structures have revealed that the Sema domain folds in the manner of the (3 propeller topology which is also found in integrins or the low-density lipoprotein (LDL) receptors. Sema domains are found in semaphorins, plexins and in the receptor tyrosine kinases Met and Ron. 

Approximately 90% of CF patients carry a loss-of-function CFTR mutation on at least one allele that results in deletion of phenylalanine 508 (F508del) in the first CFTR nucleotide-binding domain [7]. The F508del prevents the proper domain folding and assembly of the multidomain CFTR protein during its biogenesis in the endoplasmic... 

The probability that an improvement in the fit compared to the isotropic model could occur by chance is 2xl0-13. The rotational diffusion axis is oriented along the a-helix axis, and the angle between the two is about 20°. This plot also illustrates a clear separation between two sets of NH vectors, those belonging to the helix (hence oriented nearly parallel to the diffusion axis) and those in the /7-strands. Because of the architecture of the PH domain fold, the latter NH vectors are almost all orthogonal to the helix and hence to the diffusion axis. 

SuEE, S., Misea, S., Saidi, L. F., and Hurley, J. H., Structure of the GAT domain of human GGAl a syntaxin amino-terminal domain fold in an endosomal trafScking adaptor, Proc. Natl. Acad. Sci. USA, 2003, 100, 4451. 

A landmark achievement in RNA structure determination was the solution of the crystal structure of the 160 nucleotide long P4-P6 domain of the Tetrahyme-na group I intron [19,34,35,39]. The P4-P6-domain folds into a compact structure with a sharp turn that is stabilized by tight packing of the heHces. This newly discovered structural element was designated as the ribose-zipper because of the hydrogen bonds between ribose residues of the helices that participate in the structure. In addition, stabiHzation of RNA folds in P4-P6 occurs mainly via... 

GxG), motif II (YxG), motif III (RFINHxCxPN) and motif IV (ELxFDY where x is any amino acid). The conserved domain folds into several small -sheets that surround a knot-like structure to which additional domains (pre-SET (or nSET), post-SET (or cSET)) or an insertion domain (i-SET) may be added (Figure 2.5). 

There are five classes of flavin-binding structural folds presented in Table 1 that are identified by the prototype protein in which they were first discovered. These are flavodoxin (FDX), ferredoxin reductase (FNR), triosephosphate isomerase (TIM), glutathione reductase (GR) and p-cresol methylhydroxylase (PCMH). The topologies of four of these five domains are shown in Figure 2. There are also four classes of primary acceptor/donor domain folds that are identified by the prototype protein where they were first discovered. They are cytochrome P450BMP (BMP), cytochrome b5 (CYTB5), cytochrome c (CYTC) and the 2Fe-2S plant-type ferredoxin (FDN). 

Whether the core was T=3 or T=4 had been a contentious issue, in part because it is possible to prepare, in vitro, core particles of smaller diameter (330 A) than in vivo (410 A) (Coombs and Brown, 1987a,b Enzmann and Weiland, 1979 Fuller, 1987 Fuller and Argos, 1987 Horzinek and Mussgay, 1969). With determination of the domain fold, it was possible to build models of the entire core, and to show that the T=3 proposed assembly would leave unreasonable gaps between the protomers (Choi et al, 1991). 

The WD-repeat-containing proteins form a very large family that is diverse in both its function and domain structure. Within all these proteins the WD-repeat domains are thought to have two common features the domain folds into a beta propeller and the domains form a platform without any catalytic activity on which multiple protein complexes assemble reversibly. The fact that these proteins play such key roles in the formation of protein-protein complexes in nearly all the major pathways and organelles unique to eukaryotic cells has two important implications. It supports both their ancient and proto eukaryotic origins and supports a likely association with many genetic diseases. 

In order to determine a generic relation between p and r, three additional single-domain folds representative of protein topologies were also analyzed SH3-domain, ubiquitin, and /.-repressor, as indicated above. 

Ensign, D.L., Pande, V.S. The Fip35 WW domain folds with structural and mechanistic heterogeneity in molecular dynamics simulations. Biophys. J. 2009, 96, L53-5. 

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