5C8S

Crystal structure of the SARS coronavirus nsp14-nsp10 complex with functional ligands SAH and GpppA

5C8S の概要

• エントリーDOI: 10.2210/pdb5c8s/pdb
• 関連するPDBエントリー: 5C8T 5C8U
• 分子名称: Non-structural protein 10, Guanine-N7 methyltransferase, ZINC ION, ... (6 entities in total)
• 機能のキーワード: nsp14, nsp10, exoribonuclease, methyltransferase, transferase
• 由来する生物種: Human SARS coronavirus (SARS-CoV); 詳細
• 細胞内の位置: Papain-like proteinase: Host membrane; Multi-pass membrane protein. Non-structural protein 4: Host membrane; Multi-pass membrane protein. Non-structural protein 6: Host membrane ; Multi-pass membrane protein . Non-structural protein 7: Host cytoplasm, host perinuclear region . Non-structural protein 8: Host cytoplasm, host perinuclear region . Non-structural protein 9: Host cytoplasm, host perinuclear region . Non-structural protein 10: Host cytoplasm, host perinuclear region . Helicase: Host endoplasmic reticulum-Golgi intermediate compartment . Uridylate-specific endoribonuclease: Host cytoplasm, host perinuclear region : P0C6X7 P0C6X7
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 153488.05

構造登録者

Ma, Y.Y.,Wu, L.J.,Zhang, R.G.,Rao, Z.H. (登録日: 2015-06-26, 公開日: 2015-07-15, 最終更新日: 2024-11-06)

主引用文献

Ma, Y.Y.,Wu, L.J.,Shaw, N.,Gao, Y.,Wang, J.,Sun, Y.N.,Lou, Z.Y.,Yan, L.M.,Zhang, R.G.,Rao, Z.H.
Structural basis and functional analysis of the SARS coronavirus nsp14-nsp10 complex
Proc.Natl.Acad.Sci.USA, 112:9436-9441, 2015

PubMed Abstract: Nonstructural protein 14 (nsp14) of coronaviruses (CoV) is important for viral replication and transcription. The N-terminal exoribonuclease (ExoN) domain plays a proofreading role for prevention of lethal mutagenesis, and the C-terminal domain functions as a (guanine-N7) methyl transferase (N7-MTase) for mRNA capping. The molecular basis of both these functions is unknown. Here, we describe crystal structures of severe acute respiratory syndrome (SARS)-CoV nsp14 in complex with its activator nonstructural protein10 (nsp10) and functional ligands. One molecule of nsp10 interacts with ExoN of nsp14 to stabilize it and stimulate its activity. Although the catalytic core of nsp14 ExoN is reminiscent of proofreading exonucleases, the presence of two zinc fingers sets it apart from homologs. Mutagenesis studies indicate that both these zinc fingers are essential for the function of nsp14. We show that a DEEDh (the five catalytic amino acids) motif drives nucleotide excision. The N7-MTase domain exhibits a noncanonical MTase fold with a rare β-sheet insertion and a peripheral zinc finger. The cap-precursor guanosine-P3-adenosine-5',5'-triphosphate and S-adenosyl methionine bind in proximity in a highly constricted pocket between two β-sheets to accomplish methyl transfer. Our studies provide the first glimpses, to our knowledge, into the architecture of the nsp14-nsp10 complex involved in RNA viral proofreading.

PubMed: 26159422
DOI: 10.1073/pnas.1508686112

実験手法

X-RAY DIFFRACTION (3.326 Å)