PR-39, a proline-rich antibacterial peptide that inhibits phagocyte NADPH oxidase activity by binding to Src homology 3 domains of p47(phox)
PR-39, a proline-rich antibacterial peptide that inhibits phagocyte NADPH oxidase activity by binding to Src homology 3 domains of p47(phox)
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DOI：
10.1073/pnas.93.12.6014
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发表时间：
1996-06-11
影响因子：
11.1
通讯作者：
Blecha, F
中科院分区：
文献类型：
--
作者：
Shi, JS;Ross, CR;Blecha, F
由吞噬细胞NADPH氧化酶产生的活性氧中间体是宿主防御的重要组成部分，然而，这些高毒性氧化剂在炎症过程中会引起显著的组织损伤；因此，它们的生成和失活受到严格调控是至关重要的。我们在这里展示了一种内源性富含脯氨酸-精氨酸（PR）的抗菌肽PR-39，通过与细胞质成分的Src同源3结构域相互作用，通过阻断该酶的组装来抑制NADPH氧化酶的活性。这种中性粒细胞衍生的肽抑制了中性粒细胞在全细胞和NADPH氧化酶的氧依赖性杀微生物活性，氧化酶抑制和直接抗菌活性都在PR-39的氨基末端26残基中确定，氧化酶抑制归因于PR-39与p47（phox）胞质氧化酶组分的结合。其作用涉及到PR-39的多碱基氨基末端和富含脯氨酸的核心区域，这些区域与p47(phox) Src同源3结构域结合，从而抑制与细胞色素b（558）小亚基p22（phox）的相互作用。这些研究结果表明，PR-39参与组织修复过程，是一种可以调节NADPH氧化酶产生超氧阴离子的多功能肽（0(2)）。-))，从而限制炎症期间过度的组织损伤。
Reactive oxygen intermediates generated by the phagocyte NADPH oxidase are critically important components of host defense, However, these highly toxic oxidants can cause significant tissue injury during inflammation; thus, it is essential that their generation and inactivation are tightly regulated, We show here that an endogenous proline-arginine (PR)-rich antibacterial peptide, PR-39, inhibits NADPH oxidase activity by blocking assembly of this enzyme through interactions with Src homology 3 domains of a cytosolic component. This neutrophil-derived peptide inhibited oxygen-dependent microbicidal activity of neutrophils in whole cells and in a cell-free assay of NADPH oxidase, Both oxidase inhibitory and direct antimicrobial activities were defined within the amino-terminal 26 residues of PR-39, Oxidase inhibition was attributed to binding of PR-39 to the p47(phox) cytosolic oxidase component, Its effects involve both a polybasic amino-terminal segment and a proline-rich core region of PR-39 that binds to the p47(phox) Src, homology 3 domains and, thereby, inhibits interaction with the smalt subunit of cytochrome b(558), p22(phox) These findings suggest that PR-39, which has been shown to be involved in tissue repair processes, is a multifunctional peptide that can regulate NADPH oxidase production of superoxide anion (0(2)(.-)), thus limiting excessive tissue damage during inflammation.