Structural basis for the role of serine-rich repeat proteins from Lactobacillus reuteri in gut microbe-host interactions.
Structural basis for the role of serine-rich repeat proteins from Lactobacillus reuteri in gut microbe-host interactions.
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DOI：
10.1073/pnas.1715016115
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发表时间：
2018-03-20
影响因子：
11.1
通讯作者：
Juge N
中科院分区：
文献类型：
--
作者：
Sequeira S;Kavanaugh D;MacKenzie DA;Šuligoj T;Walpole S;Leclaire C;Gunning AP;Latousakis D;Willats WGT;Angulo J;Dong C;Juge N
肠道细菌在健康和疾病中起着关键作用，但支撑它们与宿主相互作用的分子机制仍然难以捉摸。富含丝氨酸的重复序列蛋白（SRRPs）是在许多革兰氏阳性病原菌中鉴定的粘附素家族。我们先前表明，肠道中发现的有益细菌物种也表达SRRP，并且SRRP是罗伊氏乳杆菌菌株定殖小鼠的能力所必需的。在这里，我们的结构和生化数据表明，L。reuteri SRRP采用了在其他结构特征SRRP中未观察到的β-螺线管折叠，并通过pH依赖性机制作为粘附素发挥作用，为这些粘附素在肠道共生体生物膜形成中的作用提供了结构见解。罗伊氏乳杆菌是一种寄生于脊椎动物胃肠道的革兰氏阳性菌，具有显著的宿主适应性。先前对啮齿动物L.菌株的突变分析。reuteri 100- 23 C鉴定了一个编码预测的表面暴露的富含丝氨酸的重复蛋白（SRRP 100 -23）的基因，该蛋白对L.小鼠的罗伊氏生物膜形成。SRRP已成为许多病原体的一组重要的表面蛋白，但没有结构信息可在肠道细菌。本文报道了来自L. reuteri ATCC 53608，揭示了该重要粘附素家族中独特的β-螺线管折叠。SRRP 53608-BR结合宿主上皮细胞和DNA在中性pH值和识别多聚半乳糖醛酸（PGA），鼠李糖半乳糖醛酸聚糖I，或硫酸软骨素A在酸性pH值。突变证实了BR推定的结合位点的作用SRRP 53608-BR与PGA的相互作用。长链分子动力学模拟表明SRRP 53608-BR经历了pH依赖性构象变化。总之，这些发现为SRRP在宿主-微生物相互作用中的作用提供了机理见解，并为使用生物膜形成益生菌对抗临床重要病原体开辟了研究途径。
Gut bacteria play a key role in health and disease, but the molecular mechanisms underpinning their interaction with the host remain elusive. The serine-rich repeat proteins (SRRPs) are a family of adhesins identified in many Gram-positive pathogenic bacteria. We previously showed that beneficial bacterial species found in the gut also express SRRPs and that SRRP was required for the ability of Lactobacillus reuteri strain to colonize mice. Here, our structural and biochemical data reveal that L. reuteri SRRP adopts a β-solenoid fold not observed in other structurally characterized SRRPs and functions as an adhesin via a pH-dependent mechanism, providing structural insights into the role of these adhesins in biofilm formation of gut symbionts. Lactobacillus reuteri, a Gram-positive bacterial species inhabiting the gastrointestinal tract of vertebrates, displays remarkable host adaptation. Previous mutational analyses of rodent strain L. reuteri 100-23C identified a gene encoding a predicted surface-exposed serine-rich repeat protein (SRRP100-23) that was vital for L. reuteri biofilm formation in mice. SRRPs have emerged as an important group of surface proteins on many pathogens, but no structural information is available in commensal bacteria. Here we report the 2.00-Å and 1.92-Å crystal structures of the binding regions (BRs) of SRRP100-23 and SRRP53608 from L. reuteri ATCC 53608, revealing a unique β-solenoid fold in this important adhesin family. SRRP53608-BR bound to host epithelial cells and DNA at neutral pH and recognized polygalacturonic acid (PGA), rhamnogalacturonan I, or chondroitin sulfate A at acidic pH. Mutagenesis confirmed the role of the BR putative binding site in the interaction of SRRP53608-BR with PGA. Long molecular dynamics simulations showed that SRRP53608-BR undergoes a pH-dependent conformational change. Together, these findings provide mechanistic insights into the role of SRRPs in host–microbe interactions and open avenues of research into the use of biofilm-forming probiotics against clinically important pathogens.
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影响因子：
6.7
作者：
Deng L;Bensing BA;Thamadilok S;Yu H;Lau K;Chen X;Ruhl S;Sullam PM;Varki A
通讯作者：
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