Elongated structure of the outer-membrane activator of peptidoglycan synthesis LpoA: implications for PBP1A stimulation.
Elongated structure of the outer-membrane activator of peptidoglycan synthesis LpoA: implications for PBP1A stimulation.
复制标题
DOI：
10.1016/j.str.2014.04.017
复制
发表时间：
2014-07-08
期刊：
影响因子：
5.7
通讯作者：
Simorre, Jean-Pierre
中科院分区：
文献类型：
--
作者：
Jean, Nicolas L.;Bougault, Catherine M.;Lodge, Adam;Derouaux, Adeline;Callens, Gilles;Egan, Alexander J. F.;Ayala, Isabel;Lewis, Richard J.;Vollmer, Waldemar;Simorre, Jean-Pierre
细菌的细胞被膜含有应力承载肽聚糖层，其在细胞生长和分裂过程中由细胞骨架元件引导的膜锚定蛋白酶扩大。在大肠杆菌中，主要的肽聚糖合成酶PBP 1A需要外膜锚定的脂蛋白LpoA的刺激。尽管LpoA的C-末端结构域与PBP 1A相互作用以刺激其肽交联活性，但对N-末端结构域的作用知之甚少。本文报道了它的NMR结构，它采用了一个全α-螺旋折叠，包括一系列的螺旋-转角-螺旋tetratricopeptide-repeat（TPR）样基序。全长LpoA的NMR光谱揭示了C-末端结构域中的两个扩展的柔性区域和N-和C-末端结构域之间的有限的（如果有的话）柔性。分析超离心和小角X-射线散射结果与LpoA采用细长形状一致，其尺寸足以从外膜跨越通过周质与肽聚糖合酶PBP 1A相互作用。LpoA的N-末端结构域具有与TPR结构域相似的全α-螺旋折叠大肠杆菌LpoA的C-末端结构域包含两个广泛的柔性区域全长LpoA采用具有低结构域间柔性的细长结构LpoA可以跨越周质以刺激肽聚糖合酶PBP 1A Jean et al.确定LpoA N-末端结构域的NMR结构并鉴定C-末端结构域中的两个独特的柔性区域。SAXS数据表明两个结构域之间的灵活性很小，导致全长蛋白质的细长形状，这是激活肽聚糖合酶PBP 1A所需的。
The bacterial cell envelope contains the stress-bearing peptidoglycan layer, which is enlarged during cell growth and division by membrane-anchored synthases guided by cytoskeletal elements. In Escherichia coli, the major peptidoglycan synthase PBP1A requires stimulation by the outer-membrane-anchored lipoprotein LpoA. Whereas the C-terminal domain of LpoA interacts with PBP1A to stimulate its peptide crosslinking activity, little is known about the role of the N-terminal domain. Herein we report its NMR structure, which adopts an all-α-helical fold comprising a series of helix-turn-helix tetratricopeptide-repeat (TPR)-like motifs. NMR spectroscopy of full-length LpoA revealed two extended flexible regions in the C-terminal domain and limited, if any, flexibility between the N- and C-terminal domains. Analytical ultracentrifugation and small-angle X-ray scattering results are consistent with LpoA adopting an elongated shape, with dimensions sufficient to span from the outer membrane through the periplasm to interact with the peptidoglycan synthase PBP1A. LpoA’s N-terminal domain features an all-α-helical fold similar to TPR domains The C-terminal domain of E. coli LpoA contains two extensive flexible regions Full-length LpoA adopts an elongated structure with low interdomain flexibility LpoA can span the periplasm to stimulate the peptidoglycan synthase PBP1A Jean et al. determine the NMR structure of LpoA N-terminal domain and identify two unique flexible regions in the C-terminal domain. SAXS data suggest little flexibility between the two domains leading to an elongated shape for the full-length protein, required in the activation of peptidoglycan synthase PBP1A.
登录
查看更多内容
影响因子：
2.9
作者：
Vijayalakshmi, J.;Akerley, Brian J.;Saper, Mark A.
通讯作者：
Saper, Mark A.
影响因子：
64.5
作者：
Paradis-Bleau C;Markovski M;Uehara T;Lupoli TJ;Walker S;Kahne DE;Bernhardt TG
通讯作者：
Bernhardt TG
影响因子：
3.4
作者：
Schuck, P
通讯作者：
Schuck, P
影响因子：
4.8
作者：
Born, Petra;Breukink, Eefjan;Vollmer, Waldemar
通讯作者：
Vollmer, Waldemar
影响因子：
14.9
作者：
Biegert A;Mayer C;Remmert M;Söding J;Lupas AN
通讯作者：
Lupas AN