Differential activation of polymorphisms of the formyl peptide receptor by formyl peptides.
Differential activation of polymorphisms of the formyl peptide receptor by formyl peptides.
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DOI：
10.1016/j.bbadis.2007.06.001
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发表时间：
2007-09
影响因子：
6.2
通讯作者：
Mills, John S.
中科院分区：
文献类型：
--
作者：
Mills, John S.
关键词：
我们研究了两个多态位点(R190W和N192K)在病毒和甲酰肽与甲酰肽受体(FPR)结合和激活中的作用。WEDWVGWI是一种来源于猫免疫缺陷病毒膜近端区域的具有抗病毒活性的多肽，与FPR具有高亲和力。肽中的三种色氨酸都是FPR结合所必需的，正如它们对抗病毒活性是必不可少的一样[S.Gianecchini，A.Di Fenza，A.D‘Ursi，D.Matteucci，P.Rovero，M.Bendinelli，抗病毒活性和来源于猫科免疫缺陷病毒跨膜糖蛋白J.Virol膜近端外膜结构域的八肽的构象特征。77(2003)3724]。甲酰-NleWEDWVGWI对FPRW190/N192表现为弱部分激动剂，对FPRR190/K192和FPRR190/N192表现为较强部分激动剂。Foryl-NleNleWEDWVGWI对所有三种FPR均表现为完全激动剂，但对W190/N192 FPR的EC50(300±0.45 NM)远高于R190/K192 FPR(40±9.3 NM)或R190/N192(60±9.8 NM)。甲酰-MYKWPWYVWL对R190/K192和R190/N192FPR的激活比W190/N192FPR优先激活5倍。甲酰-MFEDAVAWF，一种来源于禽分枝杆菌亚种蛋白质的多肽。从金黄色葡萄球菌趋化抑制蛋白N端衍生的多肽甲酰甲硫氨酸对R190/K192和R190/N192FPR的选择性最高，∼比FPR W190/N192低10倍。因此，具有W190多态的个体检测某些甲酰肽的能力可能会降低。
We have investigated the role of two polymorphic sites (R190W and N192K) on the binding and activation of the formyl peptide receptor (FPR) by viral and formyl peptides. WEDWVGWI, a peptide with antiviral activity derived from the membrane proximal region of feline immunodeficiency virus, binds with high affinity to FPR. The three tryptophans in the peptide are all essential for FPR binding, just as they were essential for antiviral activity [S. Giannecchini, A. Di Fenza, A.M. D'Ursi, D. Matteucci, P. Rovero, M. Bendinelli, Antiviral activity and conformational features of an octapeptide derived from the membrane-proximal ectodomain of the feline immunodeficiency virus transmembrane glycoprotein, J. Virol. 77 (2003) 3724]. Formyl-NleWEDWVGWI behaved as a weak partial agonist with FPR W190/N192 but a stronger partial agonist with FPR R190/K192 and FPR R190/N192. Formyl-NleNleWEDWVGWI behaved as a full agonist toward all three FPRs but exhibited a much higher EC50 with W190/N192 FPR (300 ± 45 nM) than for R190/K192 FPR (40 ± 3 nM) or R190/N192 (60 ± 8 nM). Formyl-MYKWPWYVWL preferentially activated R190/K192 and R190/N192 FPRs by > 5 fold compared to W190/N192 FPR. Formyl-MFEDAVAWF, a peptide derived from a protein in Mycobacterium avium subsp. paratuberculosis and formyl-MFTFEPFPTN, a peptide derived from the N-terminus of chemotaxis inhibitory protein of Staphylococcus aureus with an added N-terminal formyl-methionine exhibited the greatest selectivity for R190/K192 and R190/N192 FPRs with ∼ 10 fold lower EC50s than that observed with FPR W190/N192. Thus, individuals with the W190 polymorphism may display a reduced ability to detect certain formyl peptides.
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影响因子：
4.4
作者：
Haas, PJ;de Haas, CJC;van Strijp, JAG
通讯作者：
van Strijp, JAG
影响因子：
6.7
作者：
Nibali, L.;Parkar, M.;Griffiths, G. S.
通讯作者：
Griffiths, G. S.
影响因子：
4.8
作者：
Mills, JS;Miettinen, HM;Jesaitis, AJ
通讯作者：
Jesaitis, AJ
DOI：
10.1084/jem.20031636
发表时间：
2004-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
de Haas CJ;Veldkamp KE;Peschel A;Weerkamp F;Van Wamel WJ;Heezius EC;Poppelier MJ;Van Kessel KP;van Strijp JA
通讯作者：
van Strijp JA
影响因子：
5.6
作者：
Jones, DT
通讯作者：
Jones, DT