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Characterization of G protein coupling mediated by the conserved D1343.49 of DRY motif, M2416.34, and F2516.44 residues on human CXCR1

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dc.contributor.author Han X.
dc.contributor.author Feng Y.
dc.contributor.author Chen X.
dc.contributor.author Gerard C.
dc.contributor.author Boisvert W.
dc.date.accessioned 2018-09-18T20:48:55Z
dc.date.available 2018-09-18T20:48:55Z
dc.date.issued 2015
dc.identifier.issn 2211-5463
dc.identifier.uri https://dspace.kpfu.ru/xmlui/handle/net/142440
dc.description.abstract © 2015 The Authors. CXCR1, a receptor for interleukin-8 (IL-8), plays an important role in defending against pathogen invasion during neutrophil-mediated innate immune response. Human CXCR1 is a G protein-coupled receptor (GPCR) with its characteristic seven transmembrane domains (TMs). Functional and structural analyses of several GPCRs have revealed that conserved residues on TM3 (including the highly conserved Asp-Arg-Tyr (DRY) motif) and TM6 near intracellular loops contain domains critical for G protein coupling as well as GPCR activation. The objective of this study was to elucidate the role of critical amino acid residues on TM3 near intracellular loop 2 (i2) and TM6 near intracellular loop 3 (i3), including S1323.47 (Baldwin location), D1343.49, M2416.34, and F2516.44, in G protein coupling and CXCR1 activation. The results demonstrate that mutations of D1343.49 at DRY motif of CXCR1 (D134N and D134V) completely abolished the ligand binding and functional response of the receptor. Additionally, point mutations at positions 241 and 251 between TM6 and i3 loop generated mutant receptors with modest constitutive activity via Gα15 signaling activation. Our results show that D1343.49 on the highly conserved DRY motif has a distinct role for CXCR1 compared to its homologues (CXCR2 and KSHV-GPCR) in G protein coupling and receptor activation. In addition, M2416.34 and F2516.44 along with our previously identified V2476.40 on TM6 are spatially located in a "hot spot" likely essential for CXCR1 activation. Identification of these amino acid residues may be useful for elucidating mechanism of CXCR1 activation and designing specific antagonists for the treatment of CXCR1-mediated diseases.
dc.relation.ispartofseries FEBS Open Bio
dc.subject Chemokine receptor
dc.subject Constitutive activity
dc.subject CXCR1
dc.subject G protein coupled receptor
dc.subject Gα15
dc.subject Gαi
dc.title Characterization of G protein coupling mediated by the conserved D1343.49 of DRY motif, M2416.34, and F2516.44 residues on human CXCR1
dc.type Article
dc.relation.ispartofseries-volume 5
dc.collection Публикации сотрудников КФУ
dc.relation.startpage 182
dc.source.id SCOPUS22115463-2015-5-SID84925244665


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  • Публикации сотрудников КФУ Scopus [24551]
    Коллекция содержит публикации сотрудников Казанского федерального (до 2010 года Казанского государственного) университета, проиндексированные в БД Scopus, начиная с 1970г.

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