A solution structure analysis reveals a bent collagen triple helix in the complement activation recognition molecule mannan-binding lectin.
A solution structure analysis reveals a bent collagen triple helix in the complement activation recognition molecule mannan-binding lectin.
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DOI：
10.1016/j.jbc.2022.102799
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发表时间：
2023-02
影响因子：
4.8
通讯作者：
Perkins, Stephen J.
中科院分区：
文献类型：
--
作者：
Iqbal, Hina;Fung, Ka Wai;Gor, Jayesh;Bishop, Anthony C.;Makhatadze, George I.;Brodsky, Barbara;Perkins, Stephen J.
胶原蛋白三螺旋在甘露聚糖结合凝集素（MBL）的功能中至关重要，MBL是补体激活中的寡聚识别分子。MBL胶原区域与丝氨酸蛋白酶MASP-1和MASP-2形成复合物以激活补体，并且突变导致常见的免疫缺陷。为了评价它们的结构-功能特性，我们研究了四种MBL样胶原肽的溶液结构。与对照相比，在典型的（X-Y-Gly）n重复序列中存在GQG中断大大降低了MBL胶原区域的热稳定性。实验溶液的结构数据收集使用分析超离心和小角X射线和中子散射。作为对照，我们包括两种标准的Pro-Hyp-Gly胶原蛋白肽（POG）10-13，以及三种具有代表其他胶原蛋白特征的不同（X-Y-Gly）n序列的肽。这些数据进行了定量比较，原子线性胶原模型来自晶体结构和12,000构象从分子动力学模拟。在最佳拟合的分子动力学模型中，所有四种MBL肽都不同程度地弯曲至85 °。最佳拟合的基准肽（POG）n更线性，但表现出一定程度的构象灵活性。其余三种肽显示出大部分线性溶液结构。总之，胶原螺旋不是严格线性的，三螺旋的柔性程度取决于其序列，并且具有GQG中断的三螺旋显示出明显的弯曲。MBL GQG肽中的弯曲类似于补体C1 q的胶原中的弯曲，并且可能是凝集素途径活化的关键。
Collagen triple helices are critical in the function of mannan-binding lectin (MBL), an oligomeric recognition molecule in complement activation. The MBL collagen regions form complexes with the serine proteases MASP-1 and MASP-2 in order to activate complement, and mutations lead to common immunodeficiencies. To evaluate their structure-function properties, we studied the solution structures of four MBL-like collagen peptides. The thermal stability of the MBL collagen region was much reduced by the presence of a GQG interruption in the typical (X-Y-Gly)n repeat compared to controls. Experimental solution structural data were collected using analytical ultracentrifugation and small angle X-ray and neutron scattering. As controls, we included two standard Pro-Hyp-Gly collagen peptides (POG)10-13, as well as three more peptides with diverse (X-Y-Gly)n sequences that represented other collagen features. These data were quantitatively compared with atomistic linear collagen models derived from crystal structures and 12,000 conformations obtained from molecular dynamics simulations. All four MBL peptides were bent to varying degrees up to 85o in the best-fit molecular dynamics models. The best-fit benchmark peptides (POG)n were more linear but exhibited a degree of conformational flexibility. The remaining three peptides showed mostly linear solution structures. In conclusion, the collagen helix is not strictly linear, the degree of flexibility in the triple helix depends on its sequence, and the triple helix with the GQG interruption showed a pronounced bend. The bend in MBL GQG peptides resembles the bend in the collagen of complement C1q and may be key for lectin pathway activation.
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影响因子：
56.9
作者：
BELLA, J;EATON, M;BERMAN, HM
通讯作者：
BERMAN, HM
影响因子：
8
作者：
Berisio, R;Vitagliano, L;Zagari, A
通讯作者：
Zagari, A
DOI：
10.1080/07391102.1999.10508379
发表时间：
1999-12-01
影响因子：
4.4
作者：
Gough, CA;Bhatnagar, RS
通讯作者：
Bhatnagar, RS
影响因子：
2.5
作者：
Cowieson, Nathan P.;Edwards-Gayle, Charlotte J. C.;Rambo, Robert P.
通讯作者：
Rambo, Robert P.
影响因子：
2.9
作者：
Bryan, Michael A.;Cheng, Haiming;Brodsky, Barbara
通讯作者：
Brodsky, Barbara