Cardarelli Lia, Saak Christina, Gibbs Karine A
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA.
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA
mBio. 2015 Jun 9;6(3):e00251. doi: 10.1128/mBio.00251-15.
Self- versus nonself-recognition in bacteria has been described recently through genetic analyses in multiple systems; however, understanding of the biochemical properties and mechanisms of recognition-determinant proteins remains limited. Here we extend the molecular and biochemical understanding of two recognition-determinant proteins in bacteria. We have found that a heterotypic complex is formed between two bacterial self-recognition proteins, IdsD and IdsE, the genes of which have been shown to genetically encode the determinants for strain-specific identity in the opportunistic bacterial pathogen Proteus mirabilis. This IdsD-IdsE complex forms independently of other P. mirabilis-encoded self-recognition proteins. We have also shown that the binding between IdsD and IdsE is strain- and allele-specific. The specificity for interactions is encoded within a predicted membrane-spanning subdomain within each protein that contains stretches of unique amino acids in each P. mirabilis variant. Finally, we have demonstrated that this in vitro IdsD-IdsE binding interaction correlates to in vivo population identity, suggesting that the binding interactions between IdsD and IdsE are part of a cellular pathway that underpins self-recognition behavior in P. mirabilis and drives bacterial population sociality.
Here we demonstrate that two proteins, the genes of which were genetically shown to encode determinants of self-identity in bacteria, bind in vitro in an allele-restricted interaction, suggesting that molecular recognition between these two proteins is a mechanism underpinning self-recognition behaviors in P. mirabilis. Binding specificity in each protein is encapsulated in a variable region subdomain that is predicted to span the membrane, suggesting that the interaction occurs in the cell envelope. Furthermore, conversion of binding affinities in vitro correlates with conversion of self-identity in vivo, suggesting that this molecular recognition might help to drive population behaviors.
最近通过多个系统的遗传分析描述了细菌中的自我与非自我识别；然而，对识别决定蛋白的生化特性和机制的了解仍然有限。在这里，我们扩展了对细菌中两种识别决定蛋白的分子和生化理解。我们发现两种细菌自我识别蛋白IdsD和IdsE之间形成了异源复合物，其基因已被证明在遗传上编码了机会性细菌病原体奇异变形杆菌中菌株特异性身份的决定因素。这种IdsD-IdsE复合物的形成独立于其他奇异变形杆菌编码的自我识别蛋白。我们还表明IdsD和IdsE之间的结合具有菌株和等位基因特异性。相互作用的特异性编码在每个蛋白质中预测的跨膜亚结构域内，该亚结构域在每个奇异变形杆菌变体中包含独特氨基酸序列。最后，我们证明了这种体外IdsD-IdsE结合相互作用与体内群体身份相关，这表明IdsD和IdsE之间的结合相互作用是细胞途径的一部分，该途径支撑奇异变形杆菌中的自我识别行为并驱动细菌群体社会性。
在这里，我们证明了两种蛋白质，其基因在遗传上被证明编码细菌中自我身份的决定因素，在体外以等位基因限制的相互作用结合，这表明这两种蛋白质之间的分子识别是支撑奇异变形杆菌中自我识别行为的一种机制。每种蛋白质中的结合特异性封装在一个预测跨膜的可变区域亚结构域中，这表明相互作用发生在细胞包膜中。此外，体外结合亲和力的转换与体内自我身份的转换相关，这表明这种分子识别可能有助于驱动群体行为。
