Periscope Proteins are variable-length regulators of bacterial cell surface interactions.
Periscope Proteins are variable-length regulators of bacterial cell surface interactions.
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DOI：
10.1073/pnas.2101349118
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发表时间：
2021-06-08
影响因子：
11.1
通讯作者：
Potts JR
中科院分区：
文献类型：
--
作者：
Whelan F;Lafita A;Gilburt J;Dégut C;Griffiths SC;Jenkins HT;St John AN;Paci E;Moir JWB;Plevin MJ;Baumann CG;Bateman A;Potts JR
对链球菌表面蛋白Sgo_0707的单结构域和串联结构域进行了结构分析。结合生物物理学和分子动力学模拟，结果表明，观察到的基因长度变化将导致宿主配体结合域在细菌细胞表面的差异投影。对长读DNA序列数据的分析揭示了许多其他重复的细菌表面蛋白似乎经历了基因长度的变化。我们认为这些变长“潜望镜蛋白”代表了细菌细胞表面修饰的重要机制，在感染和免疫逃避中具有潜在的作用。细胞表面的变化使细菌能够在动态环境中生存，例如人类宿主的不同生态位。在这里，我们揭示了“潜望镜蛋白”是一种通过蛋白质长度变化介导的细菌表面改变的广泛机制。高度相似的折叠结构域串联阵列可以形成细长的棒状结构；因此，结构域数量的变化决定了n端宿主配体结合结构域从细胞表面投射的距离。在新获得的长读基因组测序数据的支持下，我们提出这一类可能包含超过50种不同的蛋白质，包括那些与宿主定植和人类病原体生物膜形成有关的蛋白质。在大的多结构域蛋白中，相邻结构域之间的序列分化似乎减少了结构域间的错误折叠。潜望镜蛋白打破了这一“规则”，这表明它们的长度可变性在调节细菌与宿主表面、其他细菌和免疫系统的相互作用方面起着重要作用。
The structure of single and tandem SHIRT domains from the streptococcal surface protein Sgo_0707 were determined. In conjunction with biophysics and molecular dynamics simulations, the results show that the observed gene length variation would result in differential projection of the host ligand binding domain on the bacterial cell surface. An analysis of long-read DNA sequence data reveals many other repetitive bacterial surface proteins that appear to undergo gene length variation. We propose that these variable-length “Periscope Proteins” represent an important mechanism of bacterial cell surface modification with potential roles in infection and immune evasion. Changes at the cell surface enable bacteria to survive in dynamic environments, such as diverse niches of the human host. Here, we reveal “Periscope Proteins” as a widespread mechanism of bacterial surface alteration mediated through protein length variation. Tandem arrays of highly similar folded domains can form an elongated rod-like structure; thus, variation in the number of domains determines how far an N-terminal host ligand binding domain projects from the cell surface. Supported by newly available long-read genome sequencing data, we propose that this class could contain over 50 distinct proteins, including those implicated in host colonization and biofilm formation by human pathogens. In large multidomain proteins, sequence divergence between adjacent domains appears to reduce interdomain misfolding. Periscope Proteins break this “rule,” suggesting that their length variability plays an important role in regulating bacterial interactions with host surfaces, other bacteria, and the immune system.
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影响因子：
16.6
作者：
Gruszka, Dominika T.;Whelan, Fiona;Farrance, Oliver E.;Fung, Herman K. H.;Paci, Emanuele;Jeffries, Cy M.;Svergun, Dmitri I.;Baldock, Clair;Baumann, Christoph G.;Brockwell, David J.;Potts, Jennifer R.;Clarke, Jane
通讯作者：
Clarke, Jane
金黄色葡萄球菌全球调节剂MGRA通过控制表面蛋白表达来调节结块和毒力。
影响因子：
6.7
作者：
Crosby HA;Schlievert PM;Merriman JA;King JM;Salgado-Pabón W;Horswill AR
通讯作者：
Horswill AR
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1073/pnas.1207719109
发表时间：
2012-10-02
影响因子：
11.1
作者：
Hofmann, Hagen;Soranno, Andrea;Schuler, Benjamin
通讯作者：
Schuler, Benjamin
影响因子：
6.4
作者：
Kim, JO;Weiser, JN
通讯作者：
Weiser, JN