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I Membrane Proteins (i + membrane_protein)
Selected AbstractsExpression, crystallization and preliminary X-ray diffraction analysis of human paired Ig-like type 2 receptor , (PILR,)ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 1 2008Shigekazu Tabata Human paired immunoglobulin-like (Ig-like) type 2 receptor , (PILR,) is a type I membrane protein that is mainly expressed in immune-related cells such as monocytes, granulocytes and dendritic cells. PILR, can suppress the functions of such immune cells because it has the immunoreceptor tyrosine-based inhibitory motif (ITIM) in the intracellular region, which recruits the phosphatase Src homology-2 (SH2) domain-containing protein tyrosine phosphatase 2 (SHP-2) to inhibit phophorylations induced by activation signals. The extracellular region of human PILR, comprises one immunoglobulin superfamily V-set domain and a stalk region. The V-set domain (residues 13,131) of human PILR, was overexpressed in Escherichia coli as inclusion bodies, refolded by rapid dilution and purified. The PILR, protein was successfully crystallized at 293,K using the sitting-drop vapour-diffusion method. The crystals diffracted to 1.3,Å resolution at SPring-8 BL41XU; they belong to space group P212121, with unit-cell parameters a = 40.4, b = 45.0, c = 56.9,Å, and contain one molecule per asymmetric unit. [source] Single amino acid repeats in signal peptidesFEBS JOURNAL, Issue 15 2010abaj There has been an increasing interest in single amino acid repeats ever since it was shown that these are the cause of a variety of diseases. Although a systematic study of single amino acid repeats is challenging, they have subsequently been implicated in a number of functional roles. In general surveys, leucine runs were among the most frequent. In the present study, we present a detailed investigation of repeats in signal peptides of secreted and type I membrane proteins in comparison with their mature parts. We focus on eukaryotic species because single amino acid repeats are generally rather rare in archaea and bacteria. Our analysis of over 100 species shows that repeats of leucine (but not of other hydrophobic amino acids) are over-represented in signal peptides. This trend is most pronounced in higher eukaryotes, particularly in mammals. In the human proteome, although less than one-fifth of all proteins have a signal peptide, approximately two-thirds of all leucine repeats are located in these transient regions. Signal peptides are cleaved early from the growing polypeptide chain and then degraded rapidly. This may explain why leucine repeats, which can be toxic, are tolerated at such high frequencies. The substantial fraction of proteins affected by the strong enrichment of repeats in these transient segments highlights the bias that they can introduce for systematic analyses of protein sequences. In contrast to a general lack of conservation of single amino acid repeats, leucine repeats were found to be more conserved than the remaining signal peptide regions, indicating that they may have an as yet unknown functional role. [source] The stop transfer sequence of the human UDP-glucuronosyltransferase 1A determines localization to the endoplasmic reticulum by both static retention and retrieval mechanismsFEBS JOURNAL, Issue 4 2005Lydia Barré Human UDP-glucuronosyltransferase 1A (UGT1A) isoforms are endoplasmic reticulum (ER)-resident type I membrane proteins responsible for the detoxification of a broad range of toxic phenolic compounds. These proteins contain a C-terminal stop transfer sequence with a transmembrane domain (TMD), which anchors the protein into the membrane, followed by a short cytosolic tail (CT). Here, we investigated the mechanism of ER residency of UGT1A mediated by the stop transfer sequence by analysing the subcellular localization and sensitivity to endoglycosidases of chimeric proteins formed by fusion of UGT1A stop transfer sequence (TMD/CT) with the ectodomain of the plasma membrane CD4 reporter protein. We showed that the stop transfer sequence, when attached to C-terminus of the CD4 ectodomain was able to prevent it from being transported to the cell surface. The protein was retained in the ER indicating that this sequence functions as an ER localization signal. Furthermore, we demonstrated that ER localization conferred by the stop transfer sequence was mediated in part by the KSKTH retrieval signal located on the CT. Interestingly, our data indicated that UGT1A TMD alone was sufficient to retain the protein in ER without recycling from Golgi compartment, and brought evidence that organelle localization conferred by UGT1A TMD was determined by the length of its hydrophobic core. We conclude that both retrieval mechanism and static retention mediated by the stop transfer sequence contribute to ER residency of UGT1A proteins. [source] Identity and function of ,-secretaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2003W. Taylor Kimberly Abstract ,-Secretase catalyzes intramembrane proteolysis of various type I membrane proteins, including the amyloid-, precursor protein and the Notch receptor. Despite its importance in the pathogenesis of Alzheimer's disease and to normal development, this protease has eluded identification until only very recently. Four membrane proteins are now known to be members of the protease complex: presenilin, nicastrin, aph-1, and pen-2. Recent findings suggest that these four proteins are sufficient to reconstitute the active ,-secretase complex and that together they mediate the cell surface signaling of a variety of receptors via intramembrane proteolysis. © 2003 Wiley-Liss, Inc. [source] | ||||||||||