Glycan Conformation in the Heavily Glycosylated Protein, CEACAM1.
Glycan Conformation in the Heavily Glycosylated Protein, CEACAM1.
复制标题
DOI：
10.1021/acschembio.2c00714
复制
发表时间：
2022-12-16
影响因子：
4
通讯作者：
Prestegard, James H.
中科院分区：
文献类型：
--
作者：
Rogals, Monique J.;Eletsky, Alexander;Huang, Chin;Morris, Laura C.;Moremen, Kelley W.;Prestegard, James H.
与糖蛋白连接的聚糖有助于稳定性，介导与其他蛋白质的相互作用，并启动信号转导。对于这些过程至关重要的聚糖构象是高度可变的，并且通常被描述为对多种构象异构体进行采样。这些构象可以通过分子动力学模拟产生，更广泛地通过加速分子动力学以及其他扩展的采样方法产生。然而，实验评估的贡献，各种构象作出一个本地合奏是罕见的。在这里，我们使用长距离伪接触位移（PCS）的NMR共振同位素标记的糖蛋白，以确定其聚糖的首选构象。本研究以人癌胚抗原细胞粘附分子1的N端结构域hCEACAM 1-Ig 1为模型糖蛋白。它已被设计为包括一个镧系元素离子结合环，产生PCS，以及一组同质的三个13 C标记的N-聚糖。PCS的分析表明，优选的聚糖构象异构体与蛋白质表面具有广泛的接触。导致这种偏好的因素似乎包括GlcNAc残基的N-乙酰基甲基与蛋白质表面上的疏水表面口袋之间的相互作用。
Glycans attached to glycoproteins can contribute to stability, mediate interactions with other proteins, and initiate signal transduction. Glycan conformation, which is critical to these processes, is highly variable and often depicted as sampling a multitude of conformers. These conformers can be generated by molecular dynamics simulations, and more inclusively by accelerated molecular dynamics, as well as other extended sampling methods. However, experimental assessments of the contribution that various conformers make to a native ensemble are rare. Here, we use long-range pseudo-contact shifts (PCSs) of NMR resonances from an isotopically labeled glycoprotein to identify preferred conformations of its glycans. The N-terminal domain from human Carcinoembryonic Antigen Cell Adhesion Molecule 1, hCEACAM1-Ig1, was used as the model glycoprotein in this study. It has been engineered to include a lanthanide-ion-binding loop that generates PCSs, as well as a homogeneous set of three 13C-labeled N-glycans. Analysis of the PCSs indicates that preferred glycan conformers have extensive contacts with the protein surface. Factors leading to this preference appear to include interactions between N-acetyl methyls of GlcNAc residues and hydrophobic surface pockets on the protein surface.
登录
查看更多内容
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
5.5
作者：
Miao, Yinglong;Sinko, William;Pierce, Levi;Bucher, Denis;Walker, Ross C.;McCammon, J. Andrew
通讯作者：
McCammon, J. Andrew
影响因子：
5.5
作者：
Miao Y;Feher VA;McCammon JA
通讯作者：
McCammon JA
影响因子：
16.6
作者：
Nitz, M;Sherawat, M;Imperiali, B
通讯作者：
Imperiali, B
影响因子：
16.6
作者：
Canales, Angeles;Mallagaray, Alvaro;Jimenez-Barbero, Jesus
通讯作者：
Jimenez-Barbero, Jesus