Investigating Native Metal Ion Binding Sites in Mammalian Histidine-Rich Glycoprotein.
Investigating Native Metal Ion Binding Sites in Mammalian Histidine-Rich Glycoprotein.
复制标题
研究富含哺乳动物组氨酸的糖蛋白的天然金属离子结合位点。
DOI：
10.1021/jacs.3c00587
复制
发表时间：
2023-04-12
影响因子：
15
通讯作者：
Bode, Bela E.
中科院分区：
文献类型：
--
作者：
Ackermann, Katrin;Khazaipoul, Siavash;Wort, Joshua L.;Sobczak, Amelie I. S.;El Mkami, Hassane;Stewart, Alan J.;Bode, Bela E.
哺乳动物富组氨酸糖蛋白（HRG）是一种高度通用和丰富的血浆糖蛋白，具有多种配体，参与调节许多重要的生物学过程，包括凝血，细胞粘附和血管生成。尽管其生物医学的重要性，多结构域蛋白质的结构信息是稀疏的，尤其是由于固有的无序区域，逃避高分辨率的结构表征。二价金属离子，特别是ZnII，结合到HRG蛋白内的多个位点具有关键的功能重要性，并发挥调节作用。然而，HRG的ZnII结合位点的表征是一个挑战;它们的数量和组成以及它们的结合亲和力和化学计量目前还不完全清楚。在这项研究中，我们探讨了现代电子顺磁共振（EPR）光谱的方法支持蛋白质二级和三级结构预测组装一个整体的图片本地HRG及其与金属离子的相互作用。据我们所知，这是第一次，这套EPR技术已被应用于计数和表征内源性金属离子结合位点的天然哺乳动物蛋白质的未知结构。
Mammalian histidine-rich glycoprotein (HRG) is a highly versatile and abundant blood plasma glycoprotein with a diverse range of ligands that is involved in regulating many essential biological processes, including coagulation, cell adhesion, and angiogenesis. Despite its biomedical importance, structural information on the multi-domain protein is sparse, not least due to intrinsically disordered regions that elude high-resolution structural characterization. Binding of divalent metal ions, particularly ZnII, to multiple sites within the HRG protein is of critical functional importance and exerts a regulatory role. However, characterization of the ZnII binding sites of HRG is a challenge; their number and composition as well as their affinities and stoichiometries of binding are currently not fully understood. In this study, we explored modern electron paramagnetic resonance (EPR) spectroscopy methods supported by protein secondary and tertiary structure prediction to assemble a holistic picture of native HRG and its interaction with metal ions. To the best of our knowledge, this is the first time that this suite of EPR techniques has been applied to count and characterize endogenous metal ion binding sites in a native mammalian protein of unknown structure.
登录
查看更多内容
影响因子：
15
作者：
Endeward, Burkhard;Butterwick, Joel A.;MacKinnon, Roderick;Prisner, Thomas F.
通讯作者：
Prisner, Thomas F.
影响因子：
3.4
作者：
Ackermann K;Pliotas C;Valera S;Naismith JH;Bode BE
通讯作者：
Bode BE
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
DOI：
10.1111/jth.12771
发表时间：
2015-01
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Kassaar O;Schwarz-Linek U;Blindauer CA;Stewart AJ
通讯作者：
Stewart AJ
影响因子：
8.4
作者：
Casto J;Mandato A;Hofmann L;Yakobov I;Ghosh S;Ruthstein S;Saxena S
通讯作者：
Saxena S