CCR5

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.

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Hemokinski (C-C motiv) receptor 5 (gen/pseudogen)
Prikaz baziran na PDB 1ND8.
Dostupne strukture
2L87, 2RLL
Identifikatori
Simboli	CCR5; CC-CKR-5; CCCKR5; CD195; CKR-5; CKR5; CMKBR5; IDDM22
Vanjski ID	OMIM: 601373 MGI: 107182 HomoloGene: 37325 IUPHAR: CCR5 GeneCards: CCR5 Gene
Ontologija gena Molekularna funkcija • vezivanje aktina • aktivnost fosfatidilinozitol fosfolipaze C • aktivnost prenosnika signala • receptorska aktivnost • aktivnost G-protein spregnutog receptora • aktivnost hemokinskog receptora • proteinsko vezivanje • koreceptorska aktivnost • aktivnost C-C hemokinskog receptora • C-C hemokinsko vezivanje • vezivanje hemokinskog (C-C motiv) liganda 5 Celularna komponenta • citoplazma • endozom • ćelijska membrana • integralno sa ćelijskom membranom • spoljašnja strana ćelijske membrane • ćelijska površina Biološki proces • MAPK kaskada • hemotaksa dendritske ćelije • transport kalcijumovih jona • hemotaksa • inflamatorni respons • imunski respons • ćelijski odbrambeni respons • signalni put receptora ćelijske površine • signalni put G-protein spregnutog receptora
Ortolozi
Vrsta	Čovek	Miš
Entrez	1234	12774
Ensembl	ENSG00000160791	ENSMUSG00000079227
UniProt	P51681	P51682
RefSeq (mRNA)	NM_000579.3	NM_009917.5
RefSeq (protein)	NP_000570.1	NP_034047.2
Lokacija (UCSC)	Chr 3: 46.41 - 46.42 Mb	Chr 9: 124.04 - 124.06 Mb
PubMed pretraga

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

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

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. „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. 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

• Wilkinson D (1997). „Cofactors provide the entry keys. HIV-1”. Curr. Biol. 6 (9): 1051–3. DOI:10.1016/S0960-9822(02)70661-1. PMID 8805353.
• Broder CC, Dimitrov DS (1997). „HIV and the 7-transmembrane domain receptors”. Pathobiology 64 (4): 171–9. DOI:10.1159/000164032. PMID 9031325.
• 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.
• Esté JA (2004). „Virus entry as a target for anti-HIV intervention”. Curr. Med. Chem. 10 (17): 1617–32. DOI:10.2174/0929867033457098. PMID 12871111.
• 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.
• Zaitseva M, Peden K, Golding H (2003). „HIV coreceptors: role of structure, posttranslational modifications, and internalization in viral-cell fusion and as targets for entry inhibitors”. Biochim. Biophys. Acta 1614 (1): 51–61. DOI:10.1016/S0005-2736(03)00162-7. PMID 12873765.
• 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.
• Balistreri CR, Caruso C, Grimaldi MP, et al. (2007). „CCR5 receptor: biologic and genetic implications in age-related diseases”. Ann. N. Y. Acad. Sci. 1100: 162–72. DOI:10.1196/annals.1395.014. PMID 17460174.
• Madsen HO, Poulsen K, Dahl O, et al. (1990). „Retropseudogenes constitute the major part of the human elongation factor 1 alpha gene family”. Nucleic Acids Res. 18 (6): 1513–6. DOI:10.1093/nar/18.6.1513. PMC 330519. PMID 2183196.
• Uetsuki T, Naito A, Nagata S, Kaziro Y (1989). „Isolation and characterization of the human chromosomal gene for polypeptide chain elongation factor-1 alpha”. J. Biol. Chem. 264 (10): 5791–8. PMID 2564392.
• Whiteheart SW, Shenbagamurthi P, Chen L, et al. (1989). „Murine elongation factor 1 alpha (EF-1 alpha) is posttranslationally modified by novel amide-linked ethanolamine-phosphoglycerol moieties. Addition of ethanolamine-phosphoglycerol to specific glutamic acid residues on EF-1 alpha”. J. Biol. Chem. 264 (24): 14334–41. PMID 2569467.
• Ann DK, Wu MM, Huang T, et al. (1988). „Retinol-regulated gene expression in human tracheobronchial epithelial cells. Enhanced expression of elongation factor EF-1 alpha”. J. Biol. Chem. 263 (8): 3546–9. PMID 3346208.
• Brands JH, Maassen JA, van Hemert FJ, et al. (1986). „The primary structure of the alpha subunit of human elongation factor 1. Structural aspects of guanine-nucleotide-binding sites”. Eur. J. Biochem. 155 (1): 167–71. DOI:10.1111/j.1432-1033.1986.tb09472.x. PMID 3512269.

Povezano

• Hemokinski receptor
• Hemokini

Spoljašnje veze

• Video i tekst o otkriću CCR5-a
• „Chemokine Receptors: CCR5”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2021-01-18.
• Literatura o HIV infekcijama i CCR5-u Arhivirano 2021-01-21 na Wayback Machine-u