Nuclear Magnetic Resonance Solution Structures of Lacticin Q and Aureocin A53 Reveal a Structural Motif Conserved among Leaderless Bacteriocins with Broad-Spectrum Activity
Nuclear Magnetic Resonance Solution Structures of Lacticin Q and Aureocin A53 Reveal a Structural Motif Conserved among Leaderless Bacteriocins with Broad-Spectrum Activity
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DOI：
10.1021/acs.biochem.5b01306
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发表时间：
2016-02-02
期刊：
影响因子：
2.9
通讯作者：
Vederas, John C.
中科院分区：
文献类型：
--
作者：
Acedo, Jeella Z.;van Belkum, Marco J.;Vederas, John C.
乳酸菌素Q（LnqQ）和金黄色菌素A53（AucA）分别是来自乳酸乳球菌QU 5和金黄色葡萄球菌A53的无前导序列的细菌素：这些细菌素的特征在于不存在N-末端前导序列，并且对广泛的革兰氏阳性菌具有活性。LnqQ和AucA分别由53和51个氨基酸组成，并且具有47%的相同序列。在这项研究中，他们的三维结构进行了阐明，使用溶液核磁共振，并被证明是由四个α-螺旋，假设一个非常相似的紧凑，球状的整体折叠（均方根偏差为1.7埃），具有高度阳离子表面和疏水性的核心。LnqQ和AucA的结构类似于较短的两种组分无前导细菌素肠菌素7A和7 B，尽管序列同一性水平较低。同源性建模表明，所观察到的结构基序可能是共享的无领导细菌素与广谱活性对革兰氏阳性菌。LnqQ和AucA的解析结构也表现出与环状细菌素的一些相似性。尽管它们的总体倍数相似，但抑制研究表明LnqQ和AucA对测试的革兰氏阳性菌株具有不同的抗微生物效力，表明序列差异在它们的作用机制中起关键作用。
Lacticin Q (LnqQ) and aureocin A53 (AucA) are leaderless bacteriocins from Lactococcus lactis QU5 and Staphylococcus aureus A53, respectively: These bacteriocins are Characterized by the absence of an N-terminal leader sequence and are active against a broad range of Gram-positive bacteria. LnqQ and AucA consist of 53 and 51 amino acids, respectively, and have 47% identical sequences. In this study, their three-dimensional structures were elucidated using solution nuclear magnetic resonance and were shown to consist of four alpha-helices that assume a very similar compact, globular overall fold (root-mean-square deviation of 1.7 angstrom) with a highly cationic surface and a hydrophobic core. The structures of LnqQ and AucA resemble the shorter two component leaderless bacteriocins, enterocins 7A and 7B, despite having low levels of sequence identity. Homology modeling revealed that the observed structural motif may be shared among leaderless bacteriocins with-broad-spectrum-activity against Gram-positive organisms. The elucidated structures of LnqQ and AucA also exhibit some resemblance to circular bacteriocins. Despite their similar overall fold, inhibition studies showed that LnqQ and AucA have,different antimicrobial potency against the Gram-positive strains tested, suggesting that sequence disparities play a crucial role in their mechanisms of action.