The S-layer homology domains of Paenibacillus alvei surface protein SpaA bind to cell wall polysaccharide through the terminal monosaccharide residue.
The S-layer homology domains of Paenibacillus alvei surface protein SpaA bind to cell wall polysaccharide through the terminal monosaccharide residue.
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DOI：
10.1016/j.jbc.2022.101745
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Evans SV
中科院分区：
文献类型：
--
作者：
Legg MSG;Hager-Mair FF;Krauter S;Gagnon SML;Lòpez-Guzmán A;Lim C;Blaukopf M;Kosma P;Schäffer C;Evans SV
自组装（糖）蛋白表面层（S-层）是普遍存在的原核细胞表面结构，参与结构维持、营养物扩散、宿主粘附、毒力和其他过程，这使得它们成为生物传感器或药物输送系统等治疗和生物技术应用的有吸引力的目标。然而，释放这一潜力需要扩大我们对 S 层特性的理解，尤其是表面附着的细节。革兰氏阳性细菌的 S 层通常通过 S 层同源 (SLH) 结构域三聚体与肽聚糖连接的次生细胞壁聚合物 (SCWP) 的相互作用进行附着。肺类芽孢杆菌 S 层蛋白 SpaA (SpaASLH) 的 SLH 结构域三聚体与合成的末端 SCWP 二糖和三糖类似物的共晶结构，以及等温滴定量热法结合分析表明，虽然 SpaASLH 在其一级 (G2) 和二级 (G1) 结合位点内容纳更长的生物学相关 SCWP 配体，但末端丙酮酸化 ManNAc 部分几乎是唯一的SCWP 锚定点。结合伴随着邻近受体位点的柔性环的位移，这增强了蛋白质和配体之间的互补性，包括与末端丙酮酸部分的静电互补性。值得注意的是，丙酮酰化单糖 SCWP 片段的单独结合足以引起受体结合位点以适应更长 SCWP 片段所需的方式重排。对与蛋白质结合的较长寡糖中多种构象的观察，以及三个 SCWP 受体结合位点中两个的功能性的观察，揭示了 SpaASLH-SCWP 相互作用如何进化以适应较长的 SCWP 配体并减轻细菌 S 层粘附在生长和分裂过程中固有的张力。
Self-assembling (glyco)protein surface layers (S-layers) are ubiquitous prokaryotic cell-surface structures involved in structural maintenance, nutrient diffusion, host adhesion, virulence, and other processes, which makes them appealing targets for therapeutics and biotechnological applications as biosensors or drug delivery systems. However, unlocking this potential requires expanding our understanding of S-layer properties, especially the details of surface-attachment. S-layers of Gram-positive bacteria often are attached through the interaction of S-layer homology (SLH) domain trimers with peptidoglycan-linked secondary cell wall polymers (SCWPs). Cocrystal structures of the SLH domain trimer from the Paenibacillus alvei S-layer protein SpaA (SpaASLH) with synthetic, terminal SCWP disaccharide and trisaccharide analogs, together with isothermal titration calorimetry binding analyses, reveal that while SpaASLH accommodates longer biologically relevant SCWP ligands within both its primary (G2) and secondary (G1) binding sites, the terminal pyruvylated ManNAc moiety serves as the nearly exclusive SCWP anchoring point. Binding is accompanied by displacement of a flexible loop adjacent to the receptor site that enhances the complementarity between protein and ligand, including electrostatic complementarity with the terminal pyruvate moiety. Remarkably, binding of the pyruvylated monosaccharide SCWP fragment alone is sufficient to cause rearrangement of the receptor-binding sites in a manner necessary to accommodate longer SCWP fragments. The observation of multiple conformations in longer oligosaccharides bound to the protein, together with the demonstrated functionality of two of the three SCWP receptor-binding sites, reveals how the SpaASLH-SCWP interaction has evolved to accommodate longer SCWP ligands and alleviate the strain inherent to bacterial S-layer adhesion during growth and division.
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影响因子：
3.1
作者：
Zarschler, Kristof;Janesch, Bettina;Kainz, Birgit;Ristl, Robin;Messner, Paul;Schaeffer, Christina
通讯作者：
Schaeffer, Christina
影响因子：
3.2
作者：
Janesch, Bettina;Messner, Paul;Schaeffer, Christina
通讯作者：
Schaeffer, Christina
影响因子：
0.9
作者：
Krauter, Simon;Schaeffer, Christina;Kosma, Paul
通讯作者：
Kosma, Paul
影响因子：
3
作者：
Schäffer, C;Müller, N;Messner, P
通讯作者：
Messner, P
影响因子：
3
作者：
Pettersen, EF;Goddard, TD;Ferrin, TE
通讯作者：
Ferrin, TE