3SDL

Crystal structure of human ISG15 in complex with NS1 N-terminal region from influenza B virus, Northeast Structural Genomics Consortium Target IDs HX6481, HR2873, and OR2

3SDL の概要

• エントリーDOI: 10.2210/pdb3sdl/pdb
• 関連するPDBエントリー: 1XEQ 1Z2M
• 分子名称: Non-structural protein 1, Ubiquitin-like protein ISG15 (3 entities in total)
• 機能のキーワード: structural genomics, psi-biology, northeast structural genomics consortium, nesg, protein complex, viral protein/antiviral protein, viral protein-antiviral protein complex
• 由来する生物種: Influenza B virus; 詳細
• 細胞内の位置: Host cytoplasm : P03502; Cytoplasm : P05161
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 62407.30

構造登録者

Guan, R.,Ma, L.-C.,Krug, R.M.,Montelione, G.T.,Northeast Structural Genomics Consortium (NESG) (登録日: 2011-06-09, 公開日: 2011-07-20, 最終更新日: 2023-11-29)

主引用文献

Guan, R.,Ma, L.C.,Leonard, P.G.,Amer, B.R.,Sridharan, H.,Zhao, C.,Krug, R.M.,Montelione, G.T.
Structural basis for the sequence-specific recognition of human ISG15 by the NS1 protein of influenza B virus.
Proc.Natl.Acad.Sci.USA, 108:13468-13473, 2011

PubMed Abstract: Interferon-induced ISG15 conjugation plays an important antiviral role against several viruses, including influenza viruses. The NS1 protein of influenza B virus (NS1B) specifically binds only human and nonhuman primate ISG15s and inhibits their conjugation. To elucidate the structural basis for the sequence-specific recognition of human ISG15, we determined the crystal structure of the complex formed between human ISG15 and the N-terminal region of NS1B (NS1B-NTR). The NS1B-NTR homodimer interacts with two ISG15 molecules in the crystal and also in solution. The two ISG15-binding sites on the NS1B-NTR dimer are composed of residues from both chains, namely residues in the RNA-binding domain (RBD) from one chain, and residues in the linker between the RBD and the effector domain from the other chain. The primary contact region of NS1B-NTR on ISG15 is composed of residues at the junction of the N-terminal ubiquitin-like (Ubl) domain and the short linker region between the two Ubl domains, explaining why the sequence of the short linker in human and nonhuman primate ISG15s is essential for the species-specific binding of these ISG15s. In addition, the crystal structure identifies NS1B-NTR binding sites in the N-terminal Ubl domain of ISG15, and shows that there are essentially no contacts with the C-terminal Ubl domain of ISG15. Consequently, NS1B-NTR binding to ISG15 would not occlude access of the C-terminal Ubl domain of ISG15 to its conjugating enzymes. Nonetheless, transfection assays show that NS1B-NTR binding of ISG15 is responsible for the inhibition of interferon-induced ISG15 conjugation in cells.

PubMed: 21808041
DOI: 10.1073/pnas.1107032108

実験手法

X-RAY DIFFRACTION (2.29 Å)