Two-site recognition of Staphylococcus aureus peptidoglycan by lysostaphin SH3b
Two-site recognition of Staphylococcus aureus peptidoglycan by lysostaphin SH3b
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DOI：
10.1038/s41589-019-0393-4
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发表时间：
2020-01-01
影响因子：
14.8
通讯作者：
Mesnage, Stephane
中科院分区：
文献类型：
--
作者：
Gonzalez-Delgado, Luz S.;Walters-Morgan, Hannah;Mesnage, Stephane
溶葡萄球菌酶是一种靶向肽聚糖的溶菌酶，肽聚糖是细菌细胞被膜的基本组分。它对葡萄球菌（包括耐甲氧西林金黄色葡萄球菌）显示出非常有效的特异性活性。溶葡萄球菌酶导致快速细胞溶解并破坏生物膜，因此是根除葡萄球菌感染的首选治疗剂。溶葡萄球菌酶的C-末端SH 3b结构域识别含有五甘氨酸交联桥的肽聚糖，并且已经提出驱动葡萄球菌细胞壁的优先消化。在这里，我们阐明的分子机制支持识别的葡萄球菌肽聚糖的溶葡萄球菌酶SH 3b结构域。我们发现，pentagglycine crossbridge和肽干被识别的两个独立的结合位点位于相对两侧的SH 3b域，从而诱导SH 3b域的集群。我们提出，这种不寻常的结合机制允许协同和结构动态识别的S。金黄色葡萄球菌肽聚糖和巩固这种酶的有效溶菌活性。
Lysostaphin is a bacteriolytic enzyme targeting peptidoglycan, the essential component of the bacterial cell envelope. It displays a very potent and specific activity toward staphylococci, including methicillin-resistant Staphylococcus aureus. Lysostaphin causes rapid cell lysis and disrupts biofilms, and is therefore a therapeutic agent of choice to eradicate staphylococcal infections. The C-terminal SH3b domain of lysostaphin recognizes peptidoglycans containing a pentaglycine crossbridge and has been proposed to drive the preferential digestion of staphylococcal cell walls. Here we elucidate the molecular mechanism underpinning recognition of staphylococcal peptidoglycan by the lysostaphin SH3b domain. We show that the pentaglycine crossbridge and the peptide stem are recognized by two independent binding sites located on opposite sides of the SH3b domain, thereby inducing a clustering of SH3b domains. We propose that this unusual binding mechanism allows synergistic and structurally dynamic recognition of S. aureus peptidoglycan and underpins the potent bacteriolytic activity of this enzyme.