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Solution structure of the C-terminal SH2 domain of the human tyrosine kinase Syk complexed with a phosphotyrosine pentapeptide


, : Solution structure of the C-terminal SH2 domain of the human tyrosine kinase Syk complexed with a phosphotyrosine pentapeptide. Structure (London) 3(10): 1061-1073

Background: Recruitment of the intracellular tyrosine kinase Syk to activated immune-response receptors is a critical early step in intracellular signaling. In mast cells, Syk specifically associates with doubly phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) that are found within the IgE receptor. The mechanism by which Syk recognizes these motifs is not fully understood. Both Syk SH2 (Src homology 2) domains are required for high-affinity binding to these motifs, but the C-terminal SH2 domain (Syk-C) can function independently and can bind, in isolation, to the tyrosine-phosphorylated IgE receptor in vitro. In order to improve understanding of the cellular function of Syk, we have determined the solution structure of Syk-C complexed with a phosphotyrosine peptide derived from the gamma subunit of the IgE receptor. Results: The Syk-C:peptide structure is compared with liganded structures of both the SH2 domain of Src and the C-terminal SH2 domain of ZAP-70 (the 70 kDa zeta-associated protein). The topologies of these domains are similar, although significant differences occur in the loop regions. In the Syk-C structure, the phosphotyrosine and leucine residues of the peptide ligand interact with pockets on the protein, and the intervening residues are extended. Conclusions: Syk-C resembles. other SH2 domains in its peptide-binding interactions and overall topology, a result that is consistent with its ability to function as an independent SH2 domain in vitro. This result suggests that Syk-C plays a unique role in the intact Syk protein. The determinants of the binding affinity and selectivity of Syk-C may reside in the least-conserved structural elements that comprise the phosphotyrosine- and leucinebinding sites. These structural features can be exploited for the design of Syk-selective SH2 antagonists for the treatment of allergic disorders and asthma.

US$19.90

PMID: 8590001

DOI: 10.1016/s0969-2126(01)00242-8


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Katti, M.K.; Chandramukhi, A., 1991: Comparative evaluation of cysticercal antigens and immunoassays in the diagnosis of neurocysticercosis. Enzyme linked immunosorbent assay (ELISA), dot immunobinding assay (DIA) and passive haemagglutination assay (PHA) were evaluated for the detection of anticysticercal antibodies in cerebrospinal fluids (CSF) from neurocysticercosis (NCC) patients....

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Nichols, J.P., 1972: An evaluation of market order grade changes using covariance analysis. Market Orders often include provisions for regulating size and quality standards under which fresh fruit and vegetables may be shipped. A continuing evaluation effort must be made by market order committees in order to assess the value of such reg...

Smudski, J.W.; Sprecher, R.L.; Elliott, H.W., 1964: Convulsive Interactions Of Promethazine, Meperidine And Lidocaine. Reports occurring relative to the convulsive toxic reactions in humans of promethazine, meperidine and lidocaine prompted this study of the convulsant relationships of these agents, alone or as combinations, injected intraperitoneally in mice. The...

Pierard, J.; D.B.Rsaques, J.; Kint, A., 1960: Apropos of the "pyoderma gangraenosum" of Brunsting. Goeckerman and O'Leary (Brocq's geometric phagedenism). Archives Belges de Dermatologie et de Syphiligraphie 16: 421-443

Shuai Y.; L.Y.; Dan K.; Duan Y.; Cheng G.; Y.Z.; Yang X.; Diao Y.; Y.G.; E.A., 1988: Diagnosis of enzootic abortion in yak. Diagnosis of enzootic abortion in yak on farms in Tianjun County, Qinghai Province was reported. In 1985, 155 serum samples of yak after aborting or calving were collected, of which 45 sere were positive in complement fixation test. Chlamydozoans...

Kitagawa, M.; Takahashi, M.; Yamaguchi, S.; Inoue, M.; Ogawa, S.; Hirokawa, K.; Kamiyama, R., 1999: Expression of inducible nitric oxide synthase (NOS) in bone marrow cells of myelodysplastic syndromes. Nitric oxide (NO) is a biological mediator which is synthesized from L-arginine by a family of nitric oxide synthases (NOS). We have studied the expression of the inducible NOS (iNOS) by bone marrow cells from the patients with myelodysplastic syn...

Sisson J.B.; Wierenga P.J., 1981: Spatial variability of steady state infiltration rates as a stochastic process. Steady-state infiltration rates were measured in a field plot with infiltrometers of 5, 25 and 127 cm inside diameter. Measurements were made with the 3 ringsizes along 5 parallel transects, spaced 125 cm apart. The infiltrometers were placed adja...

Pienaar, Cj, 1970: Seed mixtures for the various sub-regions. Farming in South Africa: 46 (7) 7