Cell membranes protein association

DuPont s hybrid structure 19 [33] bears the signature of a dipeptide-based SAR on y-secretase and the reminiscent lead, which was synthesized in a matrix metalloproteinase (MMP) program. Removal of the central amide bond of the parent dipeptide, replacement of the hydroxamic acid by an amide, and introduction of a seven-membered lactam resulted in high activity and removed some of the problems associated with dipeptide lead structures. Hot labeling by photoactivation of I125-benzophenone specifically cross-linked the inhibitor to three cell-membrane proteins. 

Besides the common fluorescent probes used for studying protein structure (ANS, TNS, etc.), other labels suitable espa ially for the modification of cell surfaces and the membranes of intracellular structures have been introduced in research. ANDS, for instance, is such a label (3-azido[l, 7]napthalene disulphonate) It is used for nonspecific covalent modification of hydrophilic cell surfaces. Another is FDNB (l-fluoro-2,4-dinitrobenzen) > which is used for identifying membrane proteins associated with glucose transport in human erythrocytes. More detailed information can be found elsewhere... 

Brachner, A., Reipert, S., Foisner, R. and Gotzmann, J. (2005) LEM2 is a novel MANl-related inner nuclear membrane protein associated with A-type lamins. J. Cell Sci. 118, 5797-5810. 

Wilhelmsen, K., Litjens, S.H., Kuikman, L, Tshimbalanga, N., Janssen, H., van den Bout, I., Raymond, K. and Sonnenberg, A. (2005) Nesprin-3, a novel outer nuclear membrane protein, associates with the cytoskeletal linker protein plectin. J. Cell Biol. 171, 799-810. 

The cell membrane is associated with intrinsic and extrinsic proteins. Intrinsic proteins are globular proteins that generally span the bilayer and are held within the membrane by hydrophobic and electrostatic interactions. The proteins can form channels, carriers, or pumps that enable polar molecules to cross the membrane. 

Cell surface proteins associated with the membrane via a GPI anchor participate in the uptake of nutrients, cell adhesion, and cell-cell interactions in the immune system. In T-lymphocytes, GPI-anchored proteins participate in signal transduction processes which lead to the activation of T-lymphocytes. 

When working with red blood cell membrane proteins separated by 1-DE and analysed by mass spectrometry, T. Y. Low and collaborators were able to identify 44 polypeptides, of which only 19 were also found on 2-D gels (Low et al, 2002). Some of the proteins isolated by 1-DE were polypeptides with high hydrophobicity. Only one protein associated with a... 

Most of oncogene products that are protein kinases phosphorylate specific tyrosine residues. Examples of these are src, fps, yes and sea. RSVsrc, which occurs in Rous sarcoma virus, has been the most studied. The gene products of src, fps and yes are peripheral membrane proteins associated with the cytoplasmic surface of the plasmalemma (Fig. 11.5). Both p60 " and p60 possess specific tyrosine kinase activity but with an important functional difference, namely, that p60 " kinase activity is regulated through normal cellular mechanisms and does not transform cells, whereas kinase is readily activated and... 

Calcium-activated potassium channels. Calcium-activated potassium channels are important membrane proteins associated with a wide range of biological functions including smooth muscle neurotransmitter release, proliferation of white blood cells, red blood cell size, and many more. This channels functions by pumping out K ions when they detect Ca ions, resulting in hyperpolarisation due to subsequent calcium channel deactivation. 

Cystic fibrosis, a disease of the Caucasian population, is associated with defective CL regulation and is essentially a disorder of epithehal cells (113,114). The defect arises at several levels in the CL ion transporter, ie, the cystic fibrosis transmembrane regulation (CFTR), and is associated with defective CL transport and defective processing, whereby the protein is not correctiy incorporated into the cell membrane. The most common mutation, affecting approximately 60% of patients, is termed F 608 and designates the loss of phenylalanine at this position. This mutation appears to be at least 50,000 years old, which suggests that its survival may have had evolutionary significance (115). 

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