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CCR5 (C-C hemokinski receptor tip 5, CD195) je protein na površini belih krvnih zrnca. On je komponenta imunskog sistema koja deluje kao receptor za hemokine. Mnoge forme HIV-a, virusa koji uzrokuje AIDS, inicijalno koriste CCR5 da uđu i inficiraju ćelije domaćina. Mali broj osoba ima mutaciju poznatu kao CCR5 delta 32 na CCR5 genu, koja ih zaštićuje od tih vrsta HIV-a.

Hemokinski (C-C motiv) receptor 5 (gen/pseudogen)

Prikaz baziran na PDB 1ND8.
Dostupne strukture
2L87, 2RLL
Identifikatori
SimboliCCR5; CC-CKR-5; CCCKR5; CD195; CKR-5; CKR5; CMKBR5; IDDM22
Vanjski IDOMIM601373 MGI107182 HomoloGene37325 IUPHAR: CCR5 GeneCards: CCR5 Gene
Ortolozi
VrstaČovekMiš
Entrez123412774
EnsemblENSG00000160791ENSMUSG00000079227
UniProtP51681P51682
RefSeq (mRNA)NM_000579.3NM_009917.5
RefSeq (protein)NP_000570.1NP_034047.2
Lokacija (UCSC)Chr 3:
46.41 - 46.42 Mb
Chr 9:
124.04 - 124.06 Mb
PubMed pretraga[1][2]

Kod ljudi, CCR5 gen koji kodira CCR5 protein je lociran na kratkoj (p) ruci u poziciji 21 hromozoma 3. Pojedine populacije su nasledile Delta 32 mutaciju koja je dovela do genetičke delecije porcije CCR5 gena. Homozigotni nosioci ove mutacije su otporni na M-tropne loze HIV-1 infekcije.[1]

Funkcija uredi

CCR5 protein pripada familiji beta hemokinskih receptora, integralnih membranskih proteina.[2][3] On je G protein spregnuti receptor[2] koji deluje kao hemokinski receptor u CC hemokinskoj grupi.

Prirodni hemokinski ligandi koji se vezuju za ovaj receptor su RANTES (hemotaksni citokinski protein koji je takođe poznat kao CCL5)[4][5][6] i makrofagni inflamatorni protein (MIP) 1α i 1β (takođe poznat kao CCL3 i CCL4). On isto tako formira interakcije sa CCL3L1.[5][7]

CCR5 je predominantno izražen na T ćelijama, makrofagama, dentritskim ćelijama i mikroglijama. Smatra se da CCR5 učestvuje u inflamatornom odgovoru na infekciju, mada njegova specifična uloga u normalnim imunskim funkcijama nije potpuno razjašnjena.

Reference uredi

  1. Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Saragosti S, Lapoumeroulie C, Cognaux J, Forceille C, Muyldermans G, Verhofstede C, Burtonboy G, Georges M, Imai T, Rana S, Yi Y, Smyth RJ, Collman RG, Doms RW, Vassart G, Parmentier M (August 1996). „Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene”. Nature 382 (6593): 722–5. DOI:10.1038/382722a0. PMID 8751444. 
  2. 2,0 2,1 „Genetics Home Reference”. Arhivirano iz originala na datum 2009-09-24. Pristupljeno 2014-05-08. 
  3. Samson M, Labbe O, Mollereau C, Vassart G, Parmentier M (March 1996). „Molecular cloning and functional expression of a new human CC-chemokine receptor gene”. Biochemistry 35 (11): 3362–7. DOI:10.1021/bi952950g. PMID 8639485. 
  4. Slimani H, Charnaux N, Mbemba E, Saffar L, Vassy R, Vita C, Gattegno L (October 2003). „Interaction of RANTES with syndecan-1 and syndecan-4 expressed by human primary macrophages”. Biochim. Biophys. Acta 1617 (1-2): 80–8. DOI:10.1016/j.bbamem.2003.09.006. PMID 14637022. 
  5. 5,0 5,1 Struyf S, Menten P, Lenaerts JP, Put W, D'Haese A, De Clercq E, Schols D, Proost P, Van Damme J (July 2001). „Diverging binding capacities of natural LD78beta isoforms of macrophage inflammatory protein-1alpha to the CC chemokine receptors 1, 3 and 5 affect their anti-HIV-1 activity and chemotactic potencies for neutrophils and eosinophils”. Eur. J. Immunol. 31 (7): 2170–8. DOI:10.1002/1521-4141(200107)31:7<2170::AID-IMMU2170>3.0.CO;2-D. PMID 11449371. 
  6. Proudfoot AE, Fritchley S, Borlat F, Shaw JP, Vilbois F, Zwahlen C, Trkola A, Marchant D, Clapham PR, Wells TN (April 2001). „The BBXB motif of RANTES is the principal site for heparin binding and controls receptor selectivity”. J. Biol. Chem. 276 (14): 10620–6. DOI:10.1074/jbc.M010867200. PMID 11116158. 
  7. Miyakawa T, Obaru K, Maeda K, Harada S, Mitsuya H (February 2002). „Identification of amino acid residues critical for LD78beta, a variant of human macrophage inflammatory protein-1alpha, binding to CCR5 and inhibition of R5 human immunodeficiency virus type 1 replication”. J. Biol. Chem. 277 (7): 4649–55. DOI:10.1074/jbc.M109198200. PMID 11734558. 

Literatura uredi

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  • Choe H, Martin KA, Farzan M, et al. (1998). „Structural interactions between chemokine receptors, gp120 Env and CD4”. Semin. Immunol. 10 (3): 249–57. DOI:10.1006/smim.1998.0127. PMID 9653051. 
  • Sheppard HW, Celum C, Michael NL, et al. (2002). „HIV-1 infection in individuals with the CCR5-Delta32/Delta32 genotype: acquisition of syncytium-inducing virus at seroconversion”. J. Acquir. Immune Defic. Syndr. 29 (3): 307–13. PMID 11873082. 
  • Freedman BD, Liu QH, Del Corno M, Collman RG (2004). „HIV-1 gp120 chemokine receptor-mediated signaling in human macrophages”. Immunol. Res. 27 (2–3): 261–76. DOI:10.1385/IR:27:2-3:261. PMID 12857973. 
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  • Gallo SA, Finnegan CM, Viard M, et al. (2003). „The HIV Env-mediated fusion reaction”. Biochim. Biophys. Acta 1614 (1): 36–50. DOI:10.1016/S0005-2736(03)00161-5. PMID 12873764. 
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  • Lee C, Liu QH, Tomkowicz B, et al. (2004). „Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signaling pathways”. J. Leukoc. Biol. 74 (5): 676–82. DOI:10.1189/jlb.0503206. PMID 12960231. 
  • Yi Y, Lee C, Liu QH, et al. (2004). „Chemokine receptor utilization and macrophage signaling by human immunodeficiency virus type 1 gp120: Implications for neuropathogenesis”. J. Neurovirol. 10 Suppl 1: 91–6. PMID 14982745. 
  • Seibert C, Sakmar TP (2004). „Small-molecule antagonists of CCR5 and CXCR4: a promising new class of anti-HIV-1 drugs”. Curr. Pharm. Des. 10 (17): 2041–62. DOI:10.2174/1381612043384312. PMID 15279544. 
  • Cutler CW, Jotwani R (2006). „Oral mucosal expression of HIV-1 receptors, co-receptors, and alpha-defensins: tableau of resistance or susceptibility to HIV infection?”. Adv. Dent. Res. 19 (1): 49–51. DOI:10.1177/154407370601900110. PMID 16672549. 
  • Ajuebor MN, Carey JA, Swain MG (2006). „CCR5 in T cell-mediated liver diseases: what's going on?”. J. Immunol. 177 (4): 2039–45. PMID 16887960. 
  • Lipp M, Müller G (2006). „Shaping up adaptive immunity: the impact of CCR7 and CXCR5 on lymphocyte trafficking”. Verhandlungen der Deutschen Gesellschaft für Pathologie 87: 90–101. PMID 16888899. 
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