CCR5

Из Википедије, слободне енциклопедије
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 OMIM601373 MGI107182 HomoloGene37325 IUPHAR: CCR5 GeneCards: CCR5 Gene
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 [1] [2]

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.

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[уреди]

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[уреди]

  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. ^ а б Genetics Home Reference
  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. ^ а б 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[уреди]

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