Where is ccr5 synthesized

OriGene clones in human , mouse , rat for CCR5. Addgene plasmids for CCR5. Multi-pass membrane protein. Compartment Confidence plasma membrane 5 endosome 5 extracellular 3 nucleus 3 cytoskeleton 2 mitochondrion 2 endoplasmic reticulum 2 cytosol 2 lysosome 2 golgi apparatus 2 peroxisome 1.

HIV Life Cycle. HIV Infection. Infectious disease. Binding and entry of HIV virion. GPCR ligand binding. Peptide ligand-binding receptors. G alpha i signalling events. Peptide GPCRs. Akt Signaling. Tec Kinases Signaling.

GPCR downstream signaling. Signaling by GPCR. Signal Transduction. Chemokine receptors bind chemokines. Tocris compounds for CCR5. ApexBio compounds for CCR5. This gene is overexpressed in Whole Blood x7. Medium levels in peripheral blood leukocytes and in small intestine. Low levels in ovary and lung. Blood 3. This gene was present in the common ancestor of chordates. Orthologs for CCR5 Gene. All consequence types are included: molecular consequences e.

Variation tolerance for CCR5 Gene. Gene Damage Index Score : 4. Diabetes mellitus, insulin-dependent, 22 IDDM22 [MIM]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst.

Farber J. Rollins B. Blood 90 3 , — Wells T. Power C. Proudfoot A. Trends Pharmacol. Dean M. Carrington M.

O'Brien S. Moore J. Mahalingam S. Karupiah G. Cell Biol. Murdoch C. Finn A. Blood 95 10 , — Sharma V. Lorey S. Kielian T. Homey B. Bunemann E. Schering Res.

Found Workshop 45 , 69 — Google Preview. Sheikine Y. Hansson G. Kissner T. Gerrard B. Ivanov S. Brumme Z. Chan K. Dong W. Hogg R. O'Shaughnessy M.

Montaner J. Harrigan P. AIDS 15 17 , — Martin M. Bamshad M. Feuillet P. Begum K. Galvis M. Kostecki V. Valente A. Murthy K. Haro L. Allan J. Potential roles for haplotype and mRNA diversity, differential haplotype-specific transcriptional activity, and altered transcription factor binding to polymorphic nucleotides in the pathogenesis of HIV-1 and simian immunodeficiency virus.

Dhanda R. Geevarghese R. Catano G. Walter E. Hammer M. Mangano A. Sen L. USA 98 9 , — McNicholl J. Smith D. Qari S. Hodge T. Stephens J. Reich D. Shin H. Smith M. Winkler C. Huttley G. Allikmets R. Schriml L. Malasky M. Ramos M. Morlot S. Tzetis M. Oddoux C. DiGiovine F. Nasioulas G. Chandler D. Aseev M. Hanson M. Kalaydjieva L. Glavac D. Gasparini P. Huang Y. Paxton W. Wolinsky S.

Neumann A. Zhang L. Kang S. Ceradini D. Jin Z. Yazdanbakhsh K. Kunstman K. Erickson D. Dragon E. Landau N. Phair J. Koup R. Dalgleish A. Weiss R. Academic Press , New York. Shaheen F. Collman R. Benkirane M. Jin D. Chun R. Jeang K. Goedert J. Buchbinder S. Vittinghoff E. Gomperts E. Donfield S. Vlahov D. Kaslow R. Saah A. Rinaldo C. Detels R.

Science , — Agrawal L. Qingwen J. VanHorn-Ali Z. Nicolescu I. McDermott D. Alkhatib G. Guenthner P. Hershow R. Lal R. Dezzutti C. Ometto L. Zanchetta M. Cabrelle A. Esposito G. Mainardi M. Chieco-Bianchi L.

DeRossi A. AIDS Res. Retroviruses 15 16 , — Libert F. Cochaux P. Beckman G. Samson M. Aksenova M. Cao A. Czeizel A. Claustres M. Dela Rua C.

Ferrari M. Ferrec C. Glover G. Grinde B. Guran S. Kucinskas V. Lavinha J. Mercier B. Ogur G. Peltonen L. Rosatelli C. Schwartz M. Spitsyn V. Timar L. Beckman L. Vassart G. Lomb D. O'Brien T. Jacobson L. Hoots K. Hilgartner M.

Beecroft M. Kleeberger C. Al-Sharif F. Ollier W. Zimmerman P. Boatin B. Leitman S. Hajeer A. AIDS 14 17 , — Grimaldi R. Shindo N. Acosta A. Dourado I. Brites C. Brito I. Bou-Habib D. Galvao-Castro B. Williamson C. Loubser S. Brice B. Joubert G. Smit T. Thomas R. Visagie M. Cooper M. Vander Ryst E. AIDS 14 4 , — Papa A. Papadimitriou E. Adwan G. Clewley J. Malissiovas N. Ntoutsos I. Alexiou S. Antoniadis A. FEMS Immunol. Morner A.

Bjorndal A. Leandersson A. Albert J. Bjorling E. Jansson M. Retroviruses 18 3 , — Manes S. Mira E. Colomer R. Montero S. Real L. Gomez-Mouton C. Jimenez-Baranda S. Garzon A. Lacalle R. Harshman K. Ruiz A. Martinez-A C. Mettimano M.

Specchia M. Ianni A. Arzani D. Ricciardi G. Savi L. Romano-Spica V. Srivastava P. Helms P. Stewart D. Main M. Russell G. Thorax 58 3 , — Szalai C. Bojszko A. Beko G. Falus A. Nagy A. Kozma G. Krikovszky D. Skendros P. Boura P. Tsantas N. Debre P. Theodorou I. Promrat K. Gonzalez C. Kleiner D. Koziol D. Lessie M. Merrell M. Soza A. Heller T. Ghany M. Park Y. Alter H. Hoofnagle J. Liang T. Gastroenterology 2 , — Iversen A. Christiansen C. Attermann J. Eugen-Olsen J.

Schulman S. Berntorp E. This method for measuring the binding interaction between the N-terminal CCR5 sulfo peptides and gp is preferable to a direct binding assay because the binding of 17b to gp, unlike the interaction between CCR5 and gp, has known stoichiometry and is a well characterized process, both structurally and biochemically.

Only peptides sulfated at Tyr10, Tyr14, and Tyr15 peptide 2 , Tyr10 and Tyr14 peptide 7 , Tyr14 and Tyr15 peptide 9 , and Tyr14 peptide 5 could inhibit 17b binding to gp, albeit to variable levels, whereas peptides sulfated at Tyr10 and Tyr15 peptide 8 and Tyr15 alone peptide 6 could not. However, the most potent inhibition of antibody binding was exhibited by triply sulfated peptide 2. Together, these results suggest that Tyr14 is the most critical sulfation site for gp binding to CCR5, but that sulfation of Tyr10 and Tyr15 may further enhance gp binding affinity.

These assays are based on those previously described by Farzan and co-workers. Not unexpectedly, the overall levels of restored virus entry were markedly lower than those mediated by WT CCR5.

Together, the results of these functional studies largely mirror those from the gp binding studies Figure 2 A and suggest a critical role for sTyr14 in CCR5 in mediating HIV-1 entry and a possible additional role for sTyr10 for gp binding and entry.

The observed importance of Tyr sulfation at positions 10 and 14 is corroborated by the original complementation assays performed by Farzan and co-workers, 20 which demonstrated that a CCR5 N-terminal peptide bearing sTyr residues at positions 10 and 14 could functionally reconstitute a CCR5 variant lacking the critical N-terminal region. Dragic and co-workers have additionally demonstrated that CCR5 N-terminal peptides bearing sTyr residues at positions 10 and 14 but not the singly sulfated variants were capable of binding gpCD4 complexes.

This is consistent with saturation transfer difference STD NMR studies that have shown that sTyr14 is positioned closer to gp than sTyr10 and is thought to make a number of important hydrogen-bonding interactions through its appended sulfate group. In summary, we have developed the first solid-phase sulfation strategy to allow for the divergent and site-selective incorporation of sTyr at three possible sulfation sites in a target peptide.

By incorporating three orthogonally protected Tyr residues into a single resin-bound peptide, we were able to access a library of eight sulfoforms of an N-terminal fragment of the HIV-1 coreceptor CCR5 bearing differential sulfation at Tyr10, Tyr14, and Tyr This was achieved through iterative solid-phase deprotection s , followed by solid-phase sulfation.

This technique enabled the rapid and high-yielding construction of CCR5 variants 2 — 9. These distinct sulfoforms were subsequently utilized in the first comprehensive interrogation of the ability of CCR5 variants bearing discrete Tyr sulfate modifications at positions 10, 14, and 15 to bind gp and mediate HIV-1 entry into host cells. A number of sulfated CCR5 variants, particularly those bearing a sTyr residue at position 14, were shown to bind gp and enhance viral entry into cells expressing a truncated CCR5 coreceptor that lacks the crucial N-terminus.

The results of these studies, which were corroborated by molecular modeling studies, provide important insight into the functional role of site-specific Tyr sulfation and should prove useful in the development of CCR5 mimetics and antagonists as novel antiviral therapies.

In addition, the generality of the solid-phase synthetic methodology should facilitate the construction of other sulfopeptide and sulfoprotein libraries to interrogate the importance of Tyr sulfate modifications in a number of diverse systems, including chemokine-chemokine receptor interactions e.

For the synthesis of protected Tyr derivatives 10 , 11 , and 12 and detailed solid-phase peptide synthesis SPPS protocols for the construction of sulfo peptides 2 — 9 , see Supporting Information. The CD4deltaTM plasmid expresses recombinant soluble human CD4 lacking the transmembrane domain but which retains the cytoplasmic domain that facilitates solid-phase binding assays rsCD4, aa 1—, — Two intermediate clones were produced.

Each clone was created with an overlapping region. The construct was then subcloned into the eukaryotic expression vector pcDNA 3. Cell culture supernatants containing sCD4 were collected after 48—72 h and clarified by centrifugation to remove cellular debris. Every step was followed by four washes with 0. Dilutions of synthetic CCR5 sulfopeptides were added to the plates and incubated for 1 h. The A values were corrected for the background absorbance of substrate alone.

Data points were analyzed using GraphPad Prism Version 5. This equation describes the binding of ligand to a receptor that follows the law of mass action. B max represents the maximal binding, and K D is the concentration of ligand required to reach one-half maximal binding.

The production and titration of luciferase reporter viruses and infection of cells expressing CCR5 mutants have been described previously. Supporting Information. Author Information. Richard J. Lara R. Mary L. Nadine C. David A. Martin J. Paul R. The authors declare no competing financial interest. Elsevier B. A review. The post-translational sulfation of tyrosine residues occurs in numerous secreted and integral membrane proteins and, in many cases, plays a crucial role in controlling the interactions of these proteins with physiol.

Recent advances in the understanding of protein tyrosine sulfation have come about owing to the cloning of 2 human tyrosylprotein sulfotransferases TPST-1 and TPST-2 , the development of novel anal.

Here, the authors describe the TPST enzymes, review the major techniques available for studying the presence, location, and function of tyrosine sulfation in proteins, and discuss the biol. In particular, the authors describe the detailed evidence supporting the importance of tyrosine sulfation in the cellular adhesion function of P-selectin glycoprotein ligand-1, the leukocyte trafficking and pathogen invasion functions of chemokine receptors, and the ligand binding and activation of other G-protein-coupled receptors by complement proteins, phospholipids, and glycoprotein hormones.

The O-sulfation of specific proteins on tyrosine residues was studied using the rat pheochromocytoma cell line PC12 as a model system. In intact PC12 cells labeled with inorg. After labeling of intact PC12 cells with inorg. Peptide mapping after limited proteolysis indicated sequence homologies between p and p and between p86 and p In lysed PC12 cells, p, p, p86, and p84 were phosphorylated at serine residues by an endogenous protein kinase using [32P]ATP.

Moreover, in the cell-free prepn. This sulfation reaction, which used adenosine 3'-phosphate 5'-phospho[35S]sulfate as the sulfate donor, occurred in a particulate fraction of PC12 cells and was inhibited by 5 mM EDTA. These results demonstrate the presence in PC12 cells of a novel enzyme, designated here as a tyrosylprotein sulfotransferase and imply a role for this enzyme in the posttranslational processing of specific PC12 cell proteins.

American Chemical Society. We report the structure of a biosynthetic sulfo-hirudin complexed to thrombin solved to 1. Choe, Hyeryun; Moore, Michael J. Blackwell Publishing Ltd. Plasmodium vivax is one of four Plasmodium species that cause human malaria. Duffy binding proteins. Here the authors show that tyrosines 30 and 41 of DARC are modified by addn.

These sulfated tyrosines also participate in the assocn. In contrast, alteration of tyrosine 30 to phenylalanine interferes with the assocn. A sol. These data are consistent with a role for tyrosine sulfation in the assocn. Tyrosine sulfation is a post-translational modification of secreted and transmembrane proteins, including many GPCRs such as chemokine receptors. Most chemokine receptors contain several potentially sulfated tyrosine residues in their extracellular N-terminal regions, the initial binding site for chemokine ligands.

Sulfation of these receptors increases chemokine binding affinity and potency. Although receptor sulfation is heterogeneous, insights into the mol. Tyrosine sulfation enhances the affinity of receptor peptides for cognate chemokines in a manner dependent on the position of sulfation. Moreover, tyrosine sulfation can alter the selectivity of receptor peptides among several cognate chemokines for the same receptor.

Finally, binding to receptor sulfopeptides can modulate the oligomerization state of chemokines, thereby influencing the ability of a chemokine to activate its receptor. These results increase the motivation to investigate the structural basis by which tyrosine sulfation modulates chemokine receptor activity and the biol. American Society for Microbiology. The HIV-1 envelope glycoprotein is a trimeric complex of heterodimers composed of a surface glycoprotein, gp, and a transmembrane component, gp The assocn.

CCR5mim-Ig also stabilized the assocn. The authors' data indicate that the potency of DM1-Ig derives from its avidity for the HIV-1 envelope glycoprotein trimer and from the bidirectional induction of its receptor-mimetic components. DM1 has significant advantages over other inhibitors that target both coreceptor and CD4-binding sites, and it may serve as a lead for a new class of HIV-1 inhibitor peptides.

Chiang, Jessica J. These sulfopeptides are among the broadest and most potent CCR5-mimetic peptides described to date. Leucosulfakinin LSK -II and cholecystokinin CCK , using the O - p - methylsulphinyl benzyl serine for the selective sulphation of tyrosine Tetrahedron 48 , — Google Scholar There is no corresponding record for this reference. Protein Res. In order to gain insight into the role of the resp. TFA in the presence of m-cresol and 2-methylindole gave the desired cionin deriv.

Yields obtained by the second approach were considerably higher than those obtained with the first approach. Cionin and mono-Tyr SO3H -contg.