摘要
C5a Like Receptor2——C5L2,又称G蛋白偶联受体77(GPR77),是C5aR(CD88)亚家族成员,在氨基酸序列上与C5aR(CD88)有35%的同源性。广泛分布于全身各组织细胞,在粒细胞和未成熟树突状细胞(immature dendritic)及脾脏中有大量的表达。由于长期以来未发现其生理性配体而被称为孤儿受体(orphan receptor)。当前大量研究表明C5L2能与C5a,C3a,C4a,去精C5a(C5a des-Arg74)和去精C3a(C3a des-Arg77)结合,且与C5a des-Arg74结合能力比CD88与C5a des-Arg74高10倍。在结构、功能等方面与CD88也有很多相似之处。与CD88不同的是由于C5L2第三跨膜片断末端的DRY序列上精氨酸被亮氨酸替代,有一个更短的胞内第三环,缺乏丝氨酸/苏氨酸残基,所以不能强有力地与G蛋白偶联,和C5a结合后仅诱导转染细胞发生微弱的磷酸化,不引起细胞内钙的流动及转染细胞脱颗粒;C5L2与配体结合后不发生内化,并具有与配体缓慢的结合与解离的特性。作为过敏毒素受体,C5L2在过敏毒素C5a参与的相关疾病,如脓毒症(sepsis)、急性肺损伤(ALI)、急性呼吸窘迫综合征(ARDS)等的发生、发展以及对G蛋白偶联受体的研究都具有重要的意义。
The anaphylatoxin C5a exerts a plethora of biologic activities critical in the pathogenesis of systemic inflammatory disease. Initially, a novel orphan receptor, C5L2, was detected on PMN and immature dendritic cells without evidence of intracellular signaling. The current studies report that C5L2, belonging to a subfamily of CSa receptor, has a high affinity for C5a and C5a des Arg^34, and shares 35% amino acid identity with CSaR（CD88）. C5L2 also has a moderate affinity for anaphylatoxin C3a, C3a des-Arg^77 and CAa. Because of an amino acid alteration in the so-called DRY sequence at the end of the third transmembrane segement, C5L2 does not support degranulation or increases in intracellular Ca^2 ＋ and is not rapidly internalized or stimulated chemotaxis in resporee to ligand binding. C5L2 has a slow ligand on and off rates. These biophysical properties of the C5L2 suggest that this receptor is an anaphylatoxin-binding protein with unique liond binding and signaling properies. C5L2 plays a role in the disease involved in anapltoxin C5a and has significance for the study of G protein coupled receptor. C5L2 is also a valuable tool for studying the biological activities of C5a and C5a des Arg^74.
出处
《免疫学杂志》
CAS
CSCD
北大核心
2007年第2期229-232,共4页
Immunological Journal
基金
国家自然科学基金资助项目(30571748)
