The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes
The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes
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DOI：
10.1111/j.1432-1033.1996.0325z.x
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发表时间：
1996-06-01
期刊：
影响因子：
--
通讯作者：
Salcedo, R
中科院分区：
文献类型：
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作者：
Gudmundsson, GH;Agerberth, B;Salcedo, R
多肽FA-LL-37，以前被称为Fall-39，最初是从一个从人类骨髓库中分离出来的cDNA克隆的ORF中预测的。合成了该多肽，并发现其具有抗菌活性。我们现在已经对FA-LL-37的完整基因进行了鉴定和测序，命名为FALL39。该基因全长1963个碱基，由4个外显子组成。外显子1-3编码信号序列和凯瑟琳蛋白区域。外显子4包含成熟抗菌肽的信息。我们的结果表明，FALL39是人类基因组中唯一存在的凯瑟琳基因家族成员。在启动子和内含子2中确定了急性时相反应因子的潜在结合部位。讨论了细胞因子IL-6在调控FALL39中的可能作用。抗(FA-11-S7)IGE定位于粒细胞内，脱颗粒后从这些细胞中分离出成熟的多肽。结构分析确定该成熟多肽为LL-37。为了获得用于抗菌检测的LL-37，用二肽基肽酶I对合成的FA-LL-37进行了降解。分析表明，成熟的LL-37是一种有效的抗菌肽。
The peptide FA-LL-37, previously termed FALL-39, was originally predicted from an ORF of a cDNA clone isolated from a human bone marrow library. This peptide was synthesized and found to have antibacterial activity. We have now characterized and sequenced the complete gene for FA-LL-37, termed FALL39. It is a compact gene of 1963 bp with four exons. Exons 1-3 code for a signal sequence and the cathelin region. Exon 4 contains the information for the mature antibacterial peptide. Our results indicate that FALL39 is the only member of the cathelin gene family present in the human genome. Potential binding sites for acute-phase-response factors are identified in the promoter and in intron 2. A possible role for the cytokine interleukin-6 in the regulation of FALL39 is discussed. Anti-(FA-LL-S7) Ige located the peptide in granulocytes and we isolated the mature peptide from these cells after degranulation. Structural analysis determined the mature peptide to be LL-37. To obtain LL-37 for antibacterial assays, synthetic FA-LL-37 was degraded with dipeptidyl-peptidase I. This analysis showed that mature LL-37 is a potent antibacterial peptide.