Signaling dimerization

Nyman, T., Stenmark, P., Flodin, S., Johansson, I., Hammarstrom, M., Nordlund, P. The crystal structure of the human toll-like receptor 10 cytoplasmic domain reveals a putative signaling dimer. J Biol Chem 283 (2008) 11861-11865. 

A typical emission trace for XeF is shown in Figure 5a, for 500 Torr of xenon and 0.50 Torr of SF. This curve has several components a X-ray signal, dimer rare gas fluorescence and ionic recombination formed exciplex fluorescence. The X-ray signal followed the time profile of the 3 ns. electron pulse, and was typically only a few percent of the total emission signal. The first emission peak was also observed in irradiated pure xenon, at all wavelengths across and outside the XeF emission spectrum, and was therefore assigned to the broad xenon dimer, Xe2 fluorescence. The decay of the dimer fluorescence was typically complete within several hundred nanoseconds, and its intensity varied greatly with the xenon pressure. The second peak in the emission curve was dose-dependent, and only observed across the known XeF ... 

At first, the dimeric nature of the base isolated from 3-ethyl-2-methyl-4-phenylthiazolium was postulated via a chemical route. Indeed the adduct of ICH, on a similar 2-ethylidene base is a 2-isopropylthiazolium salt in the case of methylene base it is an anilinovinyl compound identified by its absorption spectrum and chemical reactivity (45-47). This dimeric structure of the molecule has been definitively established by its NMR spectrum. It is very similar to the base issued from 2.3-dimethyl-benzo thiazolium (48). It corresponds to 2-(3 -ethyl-4 -phenyl-2 -methylenethiazolinilydene)2-methyl-3-ethyl-4-phenylthiazoline (13). There is only one methyl signal (62 = 2.59), and two series of signals (63= 1.36-3.90, 63= 1.12-3.78) correspond to ethyl groups. Three protons attributed to positions T,5,5 are shifted to a lower field 5.93, 6.58, and 8.36 ppm. The bulk of the ten phenyl protons is at 7.3 ppm (Scheme 22). 

Fig. 1. The GP Ib-IX-V complex. The complex consists of seven transmembrane polypeptides denoted GP Iba (mol wt 145,000), GP IbP (mol wt 24,000), GPIX (mol wt 17,000) and GP V (mol wt 82,000), in a stoichiometry of 2 2 2 1. The hatched region represents the plasma membrane. The area above the hatched region represents the extracellular space that below represents the cytoplasm. The complex is a major attachment site between the plasma membrane and the cytoskeleton. Two molecules associated with the cytoplasmic domain are depicted a 14-3-3 dimer, which may mediate intracellular signaling, and actin-binding protein, which connects the complex to the cortical cytoskeleton and fixes its position and influences its function.

The structure of the dimer can be derived simply by evaluation of the cross signals in the HH COSY plot. The cycloalkene protons form two AB systems with such small shift differences that the cross signals lie within the contours of the diagonal signals. 

The chromatogram of the protein mixture should show the partial separation of serum albumin and ovalbumin with a trough of at least 30% of height between their peak signals and baseline separation between ovalbumin and cytochrome c. If present in the sample, the dimeric form of serum albumin should also appear as an individual peak signal before elution of the monomeric form. 

Heldin, C. H. (1995). Dimerization of cell surface receptors in signal transduction. Cell 80 213-223. 

Recent studies indicate that - like many other receptors - G-protein-coupled receptors may form dimers, either homodimers or dimers with another type of receptor. The role of dimer formation in the cell surface expression of receptors and in their signalling and the resultant pharmacology are currently under intensive investigation [1]. 

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