The Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled-coil.
The Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled-coil.
复制标题
DOI：
10.1038/emboj.2008.101
复制
发表时间：
2008-06-18
期刊：
影响因子：
11.4
通讯作者：
Virji, Mumtaz
中科院分区：
文献类型：
--
作者：
Conners, Rebecca;Hill, Darryl J.;Borodina, Elena;Agnew, Christopher;Daniell, Sarah J.;Burton, Nicholas M.;Sessions, Richard B.;Clarke, Anthony R.;Catto, Lucy E.;Lammie, Donna;Wess, Timothy;Brady, R. Leo;Virji, Mumtaz
卡他莫拉菌是一种普遍存在的人类特有细菌，通常与上呼吸道和下呼吸道感染有关，包括中耳炎、鼻窦炎和慢性阻塞性肺疾病。该细菌使用一种自身转运蛋白UspA1来靶向一种重要的人类细胞受体癌胚抗原相关细胞黏附分子1(CEACAM1)。利用X射线结晶学，我们发现UspA1的CEACAM1受体结合区异常地由一个延伸的棒状左手三聚体螺旋组成。UspA1和CEACAM1的N-结构域的突变和结合研究已经被用来描绘配体和受体之间的相互作用表面，并指导复合体的组装。然而，溶液散射、分子模拟和电子显微镜分析都表明，UspA1盘绕螺杆也发生了显著的弯曲。这解释了UspA1如何在远离其头部群的位置与CEACAM1结合，从而允许在感染期间更接近各自的细胞表面。
Moraxella catarrhalis is a ubiquitous human-specific bacterium commonly associated with upper and lower respiratory tract infections, including otitis media, sinusitis and chronic obstructive pulmonary disease. The bacterium uses an autotransporter protein UspA1 to target an important human cellular receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Using X-ray crystallography, we show that the CEACAM1 receptor-binding region of UspA1 unusually consists of an extended, rod-like left-handed trimeric coiled-coil. Mutagenesis and binding studies of UspA1 and the N-domain of CEACAM1 have been used to delineate the interacting surfaces between ligand and receptor and guide assembly of the complex. However, solution scattering, molecular modelling and electron microscopy analyses all indicate that significant bending of the UspA1 coiled-coil stalk also occurs. This explains how UspA1 can engage CEACAM1 at a site far distant from its head group, permitting closer proximity of the respective cell surfaces during infection.
登录
查看更多内容
影响因子：
3.6
作者：
Korotkova N;Yang Y;Le Trong I;Cota E;Demeler B;Marchant J;Thomas WE;Stenkamp RE;Moseley SL;Matthews S
通讯作者：
Matthews S
影响因子：
11.4
作者：
Nummelin, H;Merckel, MC;Goldman, A
通讯作者：
Goldman, A
影响因子：
3.7
作者：
Duquerroy S;Vigouroux A;Rottier PJ;Rey FA;Bosch BJ
通讯作者：
Bosch BJ
DOI：
10.1073/pnas.58.1.45
发表时间：
1967-01-01
影响因子：
11.1
作者：
KEGELES, G;RHODES, L;BETHUNE, JL
通讯作者：
BETHUNE, JL
影响因子：
4.4
作者：
Nordström, T;Blom, AM;Riesbeck, K
通讯作者：
Riesbeck, K