Molecular basis for interaction of the protein tyrosine kinase ZAP-70 with the T-cell receptor

Hatada, Marcos; Xiao, Lu; Laird, Ellen R.; Green, Jeremy; Morgenstern, Jay P.; Lou, Meizhen; Marr, Chris S.; Phillips, Thomas B.; Ram, Mary K.; Theriault, Kelly; Zoller, Mark J.; Karas, Jennifer L.

doi:10.1038/377032a0

Cited by 329 publications

(265 citation statements)

References 44 publications

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“…Examples of interchain dimerization to form antiparallel coiled-coils are observed in the crystal structures of the replication terminator protein of B. subtilis (20) and pilin protein of N. gonorrhoeae (21). Examples of the more common intrachain antiparallel coiled-coils have been found in several enzymes, including bacterial seryl-tRNA synthetase (22), the GreA transcript cleavage factor of E. coli (23), and the T-cell protein tyrosine kinase ZAP-70 (24). The simplicity of the dimeric coiled-coil structure makes it an ideal system to use in understanding the fundamentals of protein folding and stability and in testing the principles of de novo design for a wide range of medical applications (4).…”

Section: Two- Three- and Four-stranded Coiled-coil Motifsmentioning

confidence: 96%

α-Helical Protein Assembly Motifs

Kohn

Mant

Hodges

1997

Journal of Biological Chemistry

185

132

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Section: Two- Three- and Four-stranded Coiled-coil Motifsmentioning

confidence: 96%

α-Helical Protein Assembly Motifs

Kohn

Mant

Hodges

1997

Journal of Biological Chemistry

185

132

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“…[6,10] This is supported by the structures of tSH2 in the bound and the free states of the other member of the Syk/ZAP family kinases: ZAP-70. [11,12] In the unbound state, the two SH2 domains of ZAP-70 are far apart from each other. Upon ITAM binding, the tSH2 of ZAP-70 undergoes a large conformational change, becoming locked in a more "closed" conformation.…”

Section: Introductionmentioning

confidence: 99%

Protein Flexibility and Ligand Rigidity: A Thermodynamic and Kinetic Study of ITAM‐Based Ligand Binding to Syk Tandem SH2

et al. 2005

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The Syk tandem Src homology 2 domain (Syk tSH2) constitutes a flexible protein module involved in the regulation of Syk kinase activity. The Syk tSH2 domain is assumed to function by adapting the distance between its two SH2 domains upon bivalent binding to diphosphotyrosine ligands. A thermodynamic and kinetic analysis of ligand binding was performed by using surface plasmon resonance (SPR). Furthermore, the effect of binding on the Syk tSH2 structural dynamics was probed by hydrogen/deuterium exchange and electrospray mass spectrometry (ESI‐MS). Two ligands were studied: 1, a flexible peptide derived from the tSH2 recognition ITAM sequence at the γ chain of the FcεRI‐receptor, and 2, a ligand in which the amino acids between the two SH2 binding motifs in ligand 1 have been replaced by a rigid linker of comparable length. Both ligands display comparable affinity for Syk tSH2 at 25 °C, yet a major difference in thermodynamics is observed. Upon binding of the rigid ligand, 2, the expected entropy advantage is not realized. On the contrary, 2 binds with a considerably higher entropy price of ∼9 kcal mol−1, which is attributed to a further decrease in protein flexibility upon binding to this rigid ligand. The significant reduction in deuterium incorporation in the Syk tSH2 protein upon binding of either 1 or 2, as monitored by ESI‐MS, indicates a major reduction in protein dynamics upon binding. The results are consistent with a two‐step binding model: after an initial binding step, a rapid structural change of the protein occurs, followed by a second binding step. Such a bivalent binding model allows high affinity and fast dissociation kinetics, which are very important in transient signal‐transduction processes.

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“…The binding affinity of Shc to tyrosine phosphorylated 1 is however low, at least compared to ZAP-70 and, furthermore, Shc preferentially binds to singly rather than doubly phosphorylated ITAM (Osman et al, 1995), a situation which is not likely to occur in correctly activated cells, where all three chain ITAMs have been shown to be fully phosphorylated (Neumeister Kersh et al, 1998). Furthermore, the stable interaction between phospho-and ZAP-70 mediated by a dual interaction of the tandem SH2 domains of ZAP-70 with the two phosphotyrosine residues within the chain ITAM (Hatada et al, 1995) suggests a potential steric hindrance to the access of Shc.…”

Section: Shc In Antigen Receptor Signalingmentioning

confidence: 99%

Lymphocyte Antigen Receptor Signal Integration and Regulation by the SHC Adaptor

Baldari

Telford²

1999

Biological Chemistry

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The Shc adaptor protein transduces signals from transmembrane receptors to the Ras pathway of cell activation by providing binding sites for the recruitment to the submembrane compartment of the Grb2/ Sos G-nucleotide exchange complex. The need for Shc in this process is however unclear since Grb2 can be recruited directly to phosphotyrosine containing membrane receptors through its src-homology-2 domain. Evidence from studies in lymphocytes indicates that Shc is multifunctional and is involved in the integration of independent signals to the Ras pathway. Furthermore, Shc may be a key control point at which signaling can be modulated both by interfering signals and by feedback mechanisms. Here we review recent literature to support these functions for Shc.

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Molecular basis for interaction of the protein tyrosine kinase ZAP-70 with the T-cell receptor

Cited by 329 publications

References 44 publications

α-Helical Protein Assembly Motifs

α-Helical Protein Assembly Motifs

Protein Flexibility and Ligand Rigidity: A Thermodynamic and Kinetic Study of ITAM‐Based Ligand Binding to Syk Tandem SH2

Lymphocyte Antigen Receptor Signal Integration and Regulation by the SHC Adaptor

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