Protein with polyproline

Other negative correlations are simpler to interpret. Two functionally antagonistic enzymes, namely, protein kinases and protein phosphatases, have, to date, not been found in the same protein. Similarly, WW and SH3 domains that both bind the similar polyproline-containing substrates are never found together. This last finding, however, is curious since 216 proteins that contain either two or more WW, or two or more SH3, domains are known. Finally, it appears that proteins with domains that bind phosphoserine or phosphothreonine (FHA, fork-head-associated domains) never contain domains that bind phosphoty-rosine (SH2, PTB, and PTBI domains). This indicates that cytoplasmic signaling via phosphoserine or phosphothreonine occurs via pathways distinct from those signaling via phosphotyrosine. 

Src tyrosine kinase contains both an SH2 and an SH3 domain linked to a tyrosine kinase unit with a structure similar to other protein kinases. The phosphorylated form of the kinase is inactivated by binding of a phosphoty-rosine in the C-terminal tail to its own SH2 domain. In addition the linker region between the SH2 domain and the kinase is bound in a polyproline II conformation to the SH3 domain. These interactions lock regions of the active site into a nonproductive conformation. Dephosphorylation or mutation of the C-terminal tyrosine abolishes this autoinactivation. 

Protein-protein interaction domain that binds to polyproline motifs with the sequence PXXP. Particularly important in assembling protein complexes at activated receptors which contain intrinsic tyrosine kinases. 

The crystal structure of the peptide substrate-binding domain (140—245 of 517 residues of human al subunit) of the human type I enzyme forms 2.5 tetratricopeptide (TPR) repeat domains with five a helices (PDB accession number ITJC). The organization of tyrosine residues is suggested to be key to its interaction with the substrate peptide in a polyproline II helix. The TPR motif is composed of a 34 amino acid repeated a helical motif, and is typically involved in protein-protein interactions. The tandem repeats of TPR motifs are found in many proteins related to chaperone, cell cycle, transcription, and protein transport... 

What is the nature of the insoluble forms of the prion protein They are hard to study because of the extreme insolubility, but the conversion of a helix to (3 sheet seems to be fundamental to the process and has been confirmed for the yeast prion by X-ray diffraction.11 It has been known since the 1950s that many soluble a-helix-rich proteins can be transformed easily into a fibrillar form in which the polypeptide chains are thought to form a P sheet. The chains are probably folded into hairpin loops that form an antiparallel P sheet (see Fig. 2-ll).ii-11 For example, by heating at pH 2 insulin can be converted to fibrils, whose polarized infrared spectrum (Fig. 23-3A) indicates a cross-P structure with strands lying perpendicular to the fibril axis >mm Many other proteins are also able to undergo similar transformation. Most biophysical evidence is consistent with the cross-P structure for the fibrils, which typically have diameters of 7-12 rnn."-11 These may be formed by association of thinner 2 to 5 nm fibrils.00 However, P-helical structures have been proposed for some amyloid fibrils 3 and polyproline II helices for others. 1 11... 

One such small molecule, alanine dipeptide (Ace-Ala-NMe, AD, Figure 18-1) has often been used as a model system in studies of backbone conformational equilibrium in proteins. It is composed of an alanine unit blocked by an acetyl group at the N-terminus (Ace) and a A-methylamide group (NMe) at the C-terminus. A number of experimental [1,3,4,5,6,7] and theoretical [8,9,10,11,12,13,14,15,16,17,18, 19,20,21,22,23,24,25], studies indicate that the potential energy surface for AD in vacuum and in solution are considerably different while in the gas phase the global minimum is believed to be a C7eq structure ( -83°, t/r 73°) [16], it has only recently been shown that interaction with water favors the polyproline-H (PPn, y> -75°, t/r 150°) conformation [3,7],... 

The protein collagen, from skin and tendons, is composed of approximately 30 percent proline and hydroxyproline and 30 percent glycine. This protein has an unusual structure in which three chains, each with a conformation very similar to that of polyproline, are twisted about each other to make a triple helix. The three strands are hydrogen bonded to each other, through hydrogen bonds between the —NH of glycine residues and the — C=0 groups of the other amino acids. 

Pi positions) is more twisted than a regular /3-strand to possess the polyproline II (PPII) helix conformation. The PPII conformation is also frequently used in protein-peptide interactions such as those seen in the peptide recognition by SH3 domains (Lim et at, 1994) and class II MHC molecules (Stem et at, 1994). This conformation allows the peptide chain to twist in order to maximize the interaction of its side chains with a protein surface. As a consequence, large proportions of the side chains at the P 2 Po 3.nd Pi positions of the receptor peptides are buried at the TRAF2 interface. Therefore, in the case of TRAF2-receptor interactions, the main chain hydrogen bonds and the PPII conformation maximize both main chain and side chain interactions with the TRAF2 surface. 

Apart from salivary proteins, other proteins have been used in the tannin-protein interaction studies due to some characteristics that make them similar to PRPs, like casein, gelatin, polyproline (Jobstl et al. 2004 Calderon et al. 1968 Luck et al. 1994 Poncet-Legrand et al. 2006 Siebert et al. 1996). Although it is not a protein, the polymer polyvinylpolypyrrolidone as also been used in these studies (Hagerman and Butler 1981 Laborde et al. 2006). Recently, an electronic tongue based on protein-tannin interactions has been developed to measure astringency (Edelmann and Lendl 2002). Despite the unquestionable importance of all these works to understand the interaction between tannins and proteins, extrapolation to the real context of wine sensory should be done with care. 

The p,-ARs contain polyproline motifs within their intracellular domains, which in other proteins are known to mediate interactions with SH3 domains. Using the proline-rich third intracellular loop of the (3 r AR as bait, T ang et al. (41) identified SH3p4/p8/pl3 (also referred to as endophilin 1/2/3), a SH3 domain-containing protein family, as binding partners for (3rARs. Both in vitro and in... 

Among helical structures yet to be analyzed are the w and tt helices. Preliminary analyses have already been done on the polyproline I and polyproline 11 helices (Johnston, 1975), and these studies can provide the basis for a detailed analysis of the triple-stranded collagen helix. Since helices in proteins are found in short segments and often with distorted axes, it will be important to study the influence of such defects on the vibrational spectrum. 

---