Characterization of two novel Ly-6 genes. Protein sequence and potential structural similarity to alpha-bungarotoxin and other neurotoxins.
Characterization of two novel Ly-6 genes. Protein sequence and potential structural similarity to alpha-bungarotoxin and other neurotoxins.
复制标题
DOI：
10.4049/jimmunol.150.12.5379
复制
发表时间：
1993-06
影响因子：
4.4
通讯作者：
Tony J. Fleming;Colm O’hUigin;Thomas R. Malek
中科院分区：
文献类型：
--
作者：
Tony J. Fleming;Colm O’hUigin;Thomas R. Malek
分离与 Ly-6A.2 cDNA 交叉杂交的基因组克隆并表征其功能性 Ly-6 相关基因。两个新的 Ly-6 基因，命名为 Ly-6F.1 和 Ly-6G.1，被发现具有高核苷酸同源性 (> 或 = 70%) 以及 Ly-6A/E 和 Ly-6C 的特征性四外显子基因组织。通过基于 PCR 的检测，很容易在骨髓中发现 Ly-6G.1 mRNA，而在淋巴组织中未检测到 Ly-6F.1 mRNA。因此，Ly-6G.1代表另一种Ly-6基因，其在造血细胞中具有明显的选择性表达，与Ly-6A/E和Ly-6C不同。利用现有的成熟 Ly-6 蛋白的推导蛋白序列数据，对数据库的搜索揭示了 Ly-6 蛋白与从蛇毒中分离出的神经毒素的进化关系。两组之间的蛋白质序列保守性对于（但不限于）神经毒素中的残基具有选择性，这些残基已被发现对其三级结构很重要。根据这种关系，我们提出了 Ly-6 和 Ly-6 相关蛋白（例如 CD59）的神经毒素样结构。
Genomic clones cross-hybridizing with Ly-6A.2 cDNA were isolated and characterized for functional Ly-6-related genes. Two new Ly-6 genes, designated Ly-6F.1 and Ly-6G.1, were found to have high nucleotide homology (> or = 70%) and the characteristic four exon gene organization of Ly-6A/E and Ly-6C. By a PCR-based assay, Ly-6G.1 mRNA was readily found in bone marrow, whereas Ly-6F.1 mRNA was not detected in lymphoid tissues. Thus, Ly-6G.1 represents an additional Ly-6 gene with apparent selective expression in hematopoietic cells distinct from Ly-6A/E and Ly-6C. Using the available deduced protein sequence data for mature Ly-6 proteins, searches of the database uncovered an evolutionary relationship of Ly-6 proteins with neurotoxins isolated from snake venoms. The protein sequence conservation between the two groups was selective for, but not limited to, residues in neurotoxins that have been found to be important for their tertiary structures. From this relationship, we propose a neurotoxin-like structure for Ly-6 and Ly-6-related proteins, such as CD59.