Cooperative folding of intrinsically disordered domains drives assembly of a strong elongated protein.
Cooperative folding of intrinsically disordered domains drives assembly of a strong elongated protein.
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DOI：
10.1038/ncomms8271
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发表时间：
2015-06-01
影响因子：
16.6
通讯作者：
Clarke, Jane
中科院分区：
文献类型：
--
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
细菌利用表面蛋白质粘附到其他细菌、表面和宿主细胞上。这些蛋白质需要从细菌表面突出并抵抗显著的机械力。SasG是一种在金黄色葡萄球菌表面形成延伸原纤维并促进宿主粘附和生物膜形成的蛋白质。在这里，我们表明，虽然单体和缺乏共价交联，SasG在溶液中保持高度延伸的构象。这种延伸是通过固有无序的E结构域的专性折叠协同性介导的，所述E结构域将非相邻的G5结构域偶联，形成比结构域本身更稳定的界面。因此，与直觉相反，蛋白质的延伸似乎取决于其结构域的固有不稳定性。SasG的显著机械强度来自折叠结构域内串联排列的“钳”基序。我们的研究结果揭示了一个优雅的最小的解决方案，用于组装可变长度的单体机械抗性系绳。 葡萄球菌生物膜的形成由表面蛋白SasG促进。在这里，作者表征的结构和显着的机械强度的重复区域的SasG，并显示如何延长是通过专性折叠的无序区域内的重复单元。
Bacteria exploit surface proteins to adhere to other bacteria, surfaces and host cells. Such proteins need to project away from the bacterial surface and resist significant mechanical forces. SasG is a protein that forms extended fibrils on the surface of Staphylococcus aureus and promotes host adherence and biofilm formation. Here we show that although monomeric and lacking covalent cross-links, SasG maintains a highly extended conformation in solution. This extension is mediated through obligate folding cooperativity of the intrinsically disordered E domains that couple non-adjacent G5 domains thermodynamically, forming interfaces that are more stable than the domains themselves. Thus, counterintuitively, the elongation of the protein appears to be dependent on the inherent instability of its domains. The remarkable mechanical strength of SasG arises from tandemly arrayed ‘clamp' motifs within the folded domains. Our findings reveal an elegant minimal solution for the assembly of monomeric mechano-resistant tethers of variable length. Staphylococcal biofilm formation is promoted by the surface protein SasG. Here, the authors characterize the structure and remarkable mechanical strength of the repeat region of SasG, and show how elongation is achieved by obligate folding of the disordered regions within the repeating units.
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DOI：
10.1107/s090744491003982x
发表时间：
2011-04
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Evans PR
通讯作者：
Evans PR
影响因子：
3.6
作者：
Hung, TT;Marraffini, LA;Schneewind, O
通讯作者：
Schneewind, O
影响因子：
11.4
作者：
Hilleringmann, Markus;Ringler, Philippe;Engel, Andreas
通讯作者：
Engel, Andreas
DOI：
10.1073/pnas.0401638101
发表时间：
2004-04-27
影响因子：
11.1
作者：
Gordon, MP;Ha, T;Selvin, PR
通讯作者：
Selvin, PR
DOI：
10.1073/pnas.1208134110
发表时间：
2013-01-15
影响因子：
11.1
作者：
Conrady, Deborah G.;Wilson, Jeffrey J.;Herr, Andrew B.
通讯作者：
Herr, Andrew B.