Protein sequencing domain recognition

DNA-binding proteins contact their recognition sequences via defined structural elements, termed DNA-binding motifs (overview Pabo Sauer, 1992 Burley, 1994). DNA-binding motifs are often found in structural elements of the protein which can fold independently from the rest of the protein and therefore represent separate DNA-binding domains. They can, however, also occur within sequence elements which can not independently fold, but whose folding depends on the tertiary structure of the rest of the protein. 

Fig. 8.9. Crosslinking of signal proteins with the help of protein modnles. A hypothetical protein is shown which contains SH2, SH3, PTB and PH domains. Recognition of phosphotyrosine residues occurs with the help of SH2 or PTB domains SH3 domains bind to proline-rich sequences (Pro in Protein 3) whilst the pleckstrin homology domains (PH domains) mediate binding to phosphatidyl-inositol-phosphates (PtdInsP) in the membrane. In an idealized scheme, the modular protein can associate several proteins (Protein 1 - Protein 3) and mediate interactions between these proteins (shown as broken arrows). The PH domain helps to recruit the complex to the cell membrane favoring interactions with other membrane-associated proteins (Protein X).

PTPS (6-Pyruvoyl Tetmhydropterin Synthase). 6-Pyruvoyl tetrahy-dropterin synthase catalyzes formation of tetrahydrobiopterin biosynthesis. Tetrahydrobiopterin is a cofactor for several important enzymes, such as aromatic amino acid hydroxylases and nitric oxide synthase (57). H. pylori protein HPAG1 0913 shares homology with members of the protein domain family PTPS. H. pylori protein shares poor sequence identity of 14% with the PTPS profile at an E-value of 10 10 and covers about 95% of the length of the profile. Fold recognition results also confirm the relationship between H. pylori protein and the PTPS protein domain family. A fold recognition algorithm ensures fitness of the H. pylori protein sequence on the three-dimensional structure of PTPS from... 

The ribosomal RNAs are involved in multiple molecular interactions with both protein factors and other RNAs in addition to having an extensive intramolecular secondary structure of their own. These interactions involve not only particular sequence domains but also recognition of secondary and tertiary structural features of the RNA molecule.1-12 Un-... 

Zh. Zhang, Ch-H. Lee, V. Mandiyan, J.-P. Borg, B. Margolis, J. Schlessinger, and J. Kuryan. Sequence-specific recognition of the internalization motif of the Alzheimer s amyloid precursor protein by the XI1 PTB domain. EMBOJ, 16, 6141 6150, 1997. 

Tabk 2 lists the number ofWD-repeat protein sequences identified with high confidence within various taxonomic divisions for particular species representatives. The numbers were obtained using simple sequence pattern recognition tools followed by a fiill-length protein sequence context analysis. They are presented in terms of the number of probable WD repeats and whether or not they contain additional domains of significant length. 

The common part of the structural surface template derived from bovine yB-and pB2-crystaIlins was used to determine the domain-binding sites in mouse PA3- and pB2-aystallins. Residue properties obtained for 5 protein sequences for PA3- and pB2-ciystallins in the common part of the domain-binding site are shown in Table I. As shown in that table, residues of the common recognition... 

What does this have to do with structure prediction In fact, we would like to solve a fold recognition problem (Fig. 7.3). For each domain, we consider several million possible sequences, and identify the most favorable. These provide a signature of the 3D domain structure, or fold. Indeed, if we consider a new protein sequence, for which the 3D structure is unknown, we can compare it to our database of computed sequences. If the new sequence is similar to one or more in our database, we can infer that it will adopt the same 3D stmcture. In effect, we have identified the fold of the new sequence, and this is the first step towards structure prediction by homology modeling (above) [7]. 

Other applications of neural networks in bioinformatics include the recognition of protein sequence features such as transmembrane domains (Jacoboni et al., 2001) and recognition of features in DNA sequences (promoters (Matis et al., 1996 Nair et al., 1995), coding regions (Cai Chen,... 

It has been suggested that SH2 domains may have another biological function apart from recognition of tyrosine phosphorylated protein sequences binding to phospholipids such as phosphatidylinositols (Rameh... 

Tsai, R. Y. L., Reed, R. R. (1998). Identification of DNA recognition sequences and protein interaction domains of the multiple-Zn-finger protein Roaz. Mol Cell Biol 18, 6447-6456. 

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