Human α-Defensin 6: A Small Peptide That Self-Assembles and Protects the Host by Entangling Microbes.
Human α-Defensin 6: A Small Peptide That Self-Assembles and Protects the Host by Entangling Microbes.
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DOI：
10.1021/acs.accounts.6b00653
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发表时间：
2017-04-18
影响因子：
18.3
通讯作者：
Nolan EM
中科院分区：
文献类型：
--
作者：
Chairatana P;Nolan EM
人α-防御素6（HD 6）是一种富含半胱氨酸的32个氨基酸残基的肽，通过保护宿主的粘膜部位而促进先天免疫。这种肽在小肠潘氏细胞中作为81个残基的前体肽产生，其储存在颗粒中，并释放到管腔中。HD 6的一个不寻常的特征是它缺乏对其他人α-防御素观察到的广谱抗微生物活性。HD 6具有前所未有的自组装特性，赋予了不寻常的宿主防御功能。HD 6单体自组装成称为“纳米网”的高阶低聚物，其捕获微生物并防止侵入性病原体进入宿主细胞。这种宿主防御机制的一个可能的优点是，HD 6有助于将微生物保持在管腔中，在那里它们可以被免疫系统的其他成分杀死或清除，例如招募的中性粒细胞或排出。在这个账户中，我们报告了我们目前对HD 6的理解，并专注于自2012年Bevins及其同事首次在文献中描述HD 6纳米网以来发表的工作。首先，我们提出了解决HD 6的生物合成，储存和成熟的研究，这表明自然界使用前肽策略在空间和时间上控制小肠中HD 6纳米网的形成。随后，我们强调了结构-功能研究，为理解为什么HD 6与其他特征防御素相比表现出前所未有的自组装特性的分子基础提供了基础。最后，我们考虑阐明HD 6如何有助于粘膜免疫的功能研究。除了阻断细菌侵入宿主上皮细胞外，我们最近发现HD 6抑制机会性人类真菌病原体白色念珠菌显示的毒力特征。特别地，我们发现HD 6抑制C.白色念珠菌生物膜形成，这在念珠菌病的治疗中引起并发症。我们打算这个帐户激发进一步的生物化学，生物物理学和生物学研究，这将促进我们对粘膜免疫和宿主-微生物相互作用中HD 6的理解。
Human α-defensin 6 (HD6) is a 32-residue cysteine-rich peptide that contributes to innate immunity by protecting the host at mucosal sites. This peptide is produced in small intestinal Paneth cells as an 81-residue precursor peptide that is stored in granules, and is released into the lumen. One unusual feature of HD6 is that it lacks the broad-spectrum antimicrobial activity observed for other human α-defensins. HD6 exhibits unprecedented self-assembly properties, which confer an unusual host-defense function. HD6 monomers self-assemble into higher-order oligomers termed “nanonets,” which entrap microbes and prevent invasive pathogens from entering host cells. One possible advantage of this host-defense mechanism is that HD6 helps to keep microbes in the lumen where they can be killed or removed by other components of the immune system, such as recruited neutrophils, or excreted. In this Account, we report our current understanding of HD6 and focus on work published since 2012 when Bevins and co-workers first described HD6 nanonets in the literature. First, we present studies that address the biosynthesis, storage and maturation of HD6, which demonstrate that Nature uses a propeptide strategy to spatially and temporally control the formation of HD6 nanonets in the small intestine. We subsequently highlight structure-function studies that provide a foundation for understanding the molecular basis for why HD6 exhibits unprecedented self-assembly properties compared to other characterized defensins. Lastly, we consider functional studies that illuminate how HD6 contributes to the mucosal immunity. In addition to blocking bacterial invasion into host epithelial cells, we recently discovered that HD6 suppresses virulence traits displayed by the opportunistic human fungal pathogen Candida albicans. In particular, we found that HD6 inhibits C. albicans biofilm formation, which causes complications in the treatment of candidiasis. We intend for this Account to inspire further biochemical, biophysical, and biological investigations that will advance our understanding of HD6 in mucosal immunity and the host-microbe interaction.
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影响因子：
2.9
作者：
Chairatana, Phoom;Chiang, I-Ling;Nolan, Elizabeth M.
通讯作者：
Nolan, Elizabeth M.
影响因子：
20.3
作者：
Chalifour, A;Jeannin, P;Delneste, Y
通讯作者：
Delneste, Y
影响因子：
3.5
作者：
JONES, DE;BEVINS, CL
通讯作者：
BEVINS, CL
影响因子：
15
作者：
Chairatana, Phoom;Nolan, Elizabeth M.
通讯作者：
Nolan, Elizabeth M.
影响因子：
3.2
作者：
Giblin, LJ;Chang, CJ;Frederickson, CJ
通讯作者：
Frederickson, CJ