Structural Basis of TPR-Mediated Oligomerization and Activation of Oncogenic Fusion Kinases
文献类型：期刊论文
| 作者 | Pal, Kuntal2; Bandyopadhyay, Abhishek2; Zhou, X. Edward2; Xu, Qingping3; Marciano, David P.1; Brunzelle, Joseph S.4; Yerrum, Smitha2; Griffin, Patrick R.1; Vande Woude, George2; Melcher, Karsten2 |
| 刊名 | STRUCTURE
 |
| 出版日期 | 2017-06-06 |
| 卷号 | 25期号:6页码:867-+ |
| ISSN号 | 0969-2126 |
| DOI | 10.1016/j.str.7017.04.015 |
| 文献子类 | Article |
| 英文摘要 | The nuclear pore complex subunit TPR is found in at least five different oncogenic fusion kinases, including TPR-MET, yet how TPR fusions promote activation of kinases and their oncogenic activities remains poorly understood. Here we report the crystal structure of TPR(2-142), the MET fusion partner of oncogenic TPR-MET. TPR(2-142) contains a continuous 124-residue a helix that forms an antiparallel tetramer from two leucine zipper-containing parallel coiled coils. Remarkably, single mutations cause strikingly different conformations of the coiled coil, indicating its highly dynamic nature. We further show that fusion of TPR(2-142) to the MET intracellular domain strongly and selectively stabilizes the alpha G helix of the MET kinase domain, and mutations of only the TPR leucine zipper residues at the junction to MET, but not other leucine zipper residues, abolish kinase activation. Together, these results provide critical insight into the TPR structure and its ability to induce dimerization and activation of fusion kinases. |
| WOS关键词 | RECEPTOR TYROSINE KINASE ; PROTEIN-LIGAND INTERACTIONS ; EXCHANGE MASS-SPECTROMETRY ; GROWTH-FACTOR ; COILED COILS ; MET ONCOGENE ; EGF RECEPTOR ; DOMAIN ; AUTOINHIBITION ; REFINEMENT |
| 资助项目 | Van Andel Research Institute[00000000] ; NIH[R01 GM102545] ; NIH[GM104212] ; NIH[DK071662] ; National Natural Science Foundation of China[31300245] ; Ministry of Science and Technology (China)[2012ZX09301001] ; Ministry of Science and Technology (China)[2012CB910403] ; Ministry of Science and Technology (China)[2013CB910600] ; Ministry of Science and Technology (China)[XDB08020303] ; Ministry of Science and Technology (China)[2013ZX09507001] ; Amway (China)[00000000] ; Michigan Economic Development Corporation[00000000] ; Michigan Technology Tri-Corridor[085P1000817] ; Office of Science of the US Department of Energy,[DE-AC02-06CH11357] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000405599500008 |
| 出版者 | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272617]  |
| 专题 | 药物靶标结构与功能中心 |
| 通讯作者 | Melcher, Karsten; Xu, H. Eric |
| 作者单位 | 1.Scripps Florida, Scripps Res Inst, Translat Res Inst, Dept Mol Med, Jupiter, FL 33458 USA; 2.Van Andel Res Inst, Ctr Canc & Cell Biol, Grand Rapids, MI 49503 USA; 3.Argonne Natl Lab, GMCA Adv Photon Source, Lemont, IL 60439 USA; 4.Northwestern Univ, Synchrotron Res Ctr, Life Sci Collaborat Access Team, Dept Mol Pharmacol & Biol Chem, Argonne, IL 60439 USA; 5.Chinese Acad Sci, VARI SIMM Ctr Struct & Funct Drug Targets, Shanghai 201203, Peoples R China; 6.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Pal, Kuntal,Bandyopadhyay, Abhishek,Zhou, X. Edward,et al. Structural Basis of TPR-Mediated Oligomerization and Activation of Oncogenic Fusion Kinases[J]. STRUCTURE,2017,25(6):867-+. |
| APA | Pal, Kuntal.,Bandyopadhyay, Abhishek.,Zhou, X. Edward.,Xu, Qingping.,Marciano, David P..,...&Xu, H. Eric.(2017).Structural Basis of TPR-Mediated Oligomerization and Activation of Oncogenic Fusion Kinases.STRUCTURE,25(6),867-+. |
| MLA | Pal, Kuntal,et al."Structural Basis of TPR-Mediated Oligomerization and Activation of Oncogenic Fusion Kinases".STRUCTURE 25.6(2017):867-+. |
入库方式： OAI收割
来源：上海药物研究所
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