Switch moiety in agonist/antagonist dual effect of S19 ribosomal protein dimer on leukocyte chemotactic C5a receptor.
Switch moiety in agonist/antagonist dual effect of S19 ribosomal protein dimer on leukocyte chemotactic C5a receptor.
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S19核糖体蛋白二聚体对白细胞趋化C5a受体的激动剂/拮抗剂双重作用中的开关部分。
DOI：
10.1016/s0002-9440(10)63934-x
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Tetsurou Yamamoto
中科院分区：
文献类型：
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作者：
A. Shrestha;Megumi Shiokawa;T. Nishimura;H. Nishiura;Yuji Tanaka;N. Nishino;Y. Shibuya;Tetsurou Yamamoto
S19核糖体蛋白的交联同二聚体（RP S19）由于在白细胞趋化性中对C5 a受体的双重作用而诱导单核细胞占优势的浸润，对单核细胞是激动性的，对多形核白细胞（PMN）是拮抗性的（H. Nishiura，Y.涩谷、T. Yamamoto，Lab Invest 1998，78：1615-1623）。激动性配体部分最近被确定为-Leu 131-Asp 132-Arg 133-（Y.涩谷（Shibuya）等人，美国病理学杂志（Am J Pathol）2001，159：2293-2301）。在这项研究中，我们确定了负责拮抗功能的部分。RP S19的C-末端类似物肽，具有18个残基，其中含有激动性配体部分作为一部分，再现了白细胞趋化性的双重功能。C5 a类似物肽吸引PMN以及单核细胞。当RPS 19的C-末端12个残基在激动剂部分IAGQVAAANKKH之后连接到C5 a肽时，嵌合肽新获得了双重功能，表明RPS 19的C-末端部分作为从激动剂到拮抗剂的转换器起作用。C-末端截断分析表明，C-末端His不是必需的，但下一个Lys是必要的转换器功能。C-末端4个残基被截短的突变体RP S19的同源二聚体在体内白细胞浸润中失去了单核细胞选择性，就像在体外白细胞趋化性的情况下一样。这些结果表明RP S19二聚体从C5 a受体激动剂到拮抗剂的转化归因于Ile 134和Lys 144之间的IAGQVAAANKK部分。
The cross-linked homodimer of S19 ribosomal protein (RP S19) induces monocyte predominant infiltration due to a dual effect on the C5a receptor in leukocyte chemotaxis, agonistic to monocytes and antagonistic to polymorphonuclear leukocytes (PMN) (H. Nishiura, Y. Shibuya, T. Yamamoto, Lab Invest 1998, 78:1615–1623). The agonistic ligand moiety was recently determined to be -Leu131-Asp132-Arg133- (Y. Shibuya et al, Am J Pathol 2001, 159:2293–2301). In this study we determined the moiety responsible for the antagonistic function. A C-terminal analogue peptide of RP S19, with 18 residues containing the agonistic ligand moiety as a part, reproduced the dual function in the leukocyte chemotaxis. A C5a analogue peptide attracted PMN as well as monocytes. When C-terminal 12 residues of RP S19 after the agonistic moiety, IAGQVAAANKKH, were connected to the C5a peptide, the chimeric peptide newly obtained the dual function, indicating that the C-terminal portion of RP S19 functions as a converter from the agonist to the antagonist. C-terminal truncation analyses indicated that the C-terminal His was not essential but the next Lys was necessary for the converter function. The homodimer of a mutant RP S19 that was truncated for the C-terminal 4 residues lost the monocyte selectivity in the leukocyte infiltration in vivo as in the case of the leukocyte chemotaxis in vitro. These results indicated that the conversion of the RP S19 dimer from agonist to antagonist of C5a receptor is attributed to the IAGQVAAANKK moiety between Ile134 and Lys144.