The Proline/Glycine-Rich Region of the Biofilm Adhesion Protein Aap Forms an Extended Stalk that Resists Compaction.
The Proline/Glycine-Rich Region of the Biofilm Adhesion Protein Aap Forms an Extended Stalk that Resists Compaction.
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DOI：
10.1016/j.jmb.2016.11.017
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发表时间：
2017-01-20
影响因子：
5.6
通讯作者：
Herr AB
中科院分区：
文献类型：
--
作者：
Yarawsky AE;English LR;Whitten ST;Herr AB
表皮葡萄球菌是导致医疗保健相关感染的主要细菌菌种之一。S.表皮的一个重要特征是其形成生物膜的能力，这使得细菌对宿主免疫应答和抗生素作用具有高度抗性。生物膜内的细胞间粘附由积累相关蛋白（Aap）介导，Aap是一种以锌依赖性方式自组装的细胞壁锚定蛋白。Aap的C末端部分包含一个富含脯氨酸/甘氨酸的、长135个氨基酸的区域，该区域尚未得到表征。该区域包含一组18个几乎相同的AEPGKP重复序列。使用生物物理技术对脯氨酸/甘氨酸富集区（PGR）的分析表明，该区域是一种高度延伸的内在无序多肽（IDP），具有异常高的聚脯氨酸II型螺旋（PPII）倾向。与许多IDP相反，通过分析超离心和动态光散射测量，溶液中PGR的全局构象状态具有最小的温度依赖性。此外，在加入渗透剂TMAO或共溶剂TFE后，PCR对构象崩溃或α-螺旋形成具有抗性。总的来说，这些结果表明PGR作为弹性的延伸柄发挥作用，其将Aap的其余部分从细菌细胞壁向外投射，促进生物膜中细胞之间的细胞间粘附。这项工作揭示了通常在细菌细胞壁锚定蛋白附着点附近发现的低复杂性区域。
Staphylococcus epidermidis is one of the primary bacterial species responsible for healthcare-associated infections. The most significant virulence factor for S. epidermidis is its ability to form a biofilm, which renders the bacteria highly resistant to host immune responses and antibiotic action. Intercellular adhesion within the biofilm is mediated by the accumulation-associated protein (Aap), a cell wall-anchored protein that self-assembles in a zinc-dependent manner. The C-terminal portion of Aap contains a proline/glycine-rich, 135 amino acid-long region that has not yet been characterized. The region contains a set of 18 nearly identical AEPGKP repeats. Analysis of the proline/glycine-rich region (PGR) using biophysical techniques demonstrated the region is a highly extended, intrinsically disordered polypeptide (IDP) with unusually high polyproline type II helix (PPII) propensity. In contrast to many IDPs, there was a minimal temperature dependence of the global conformational state of PGR in solution as measured by analytical ultracentrifugation and dynamic light scattering. Furthermore, PGR was resistant to conformational collapse or α-helix formation upon addition of the osmolyte TMAO or the cosolvent TFE. Collectively, these results suggest PGR functions as a resilient, extended stalk that projects the rest of Aap outward from the bacterial cell wall, promoting intercellular adhesion between cells in the biofilm. This work sheds light on regions of low complexity often found near the attachment point of bacterial cell wall-anchored proteins.