8T2M

Crystal structure of GABARAP in complex with the LIR of NSs4

8T2M の概要

• エントリーDOI: 10.2210/pdb8t2m/pdb
• 分子名称: Non-structural protein S,Gamma-aminobutyric acid receptor-associated protein chimera (2 entities in total)
• 機能のキーワード: rift valley fever virus, autophagy, lc3, gabarap, lir, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15192.23

構造登録者

Ali, M.G.H.,Wahba, H.M.,Cyr, N.,Omichinski, J.G. (登録日: 2023-06-06, 公開日: 2024-04-03)

主引用文献

Petraccione, K.,Ali, M.G.H.,Cyr, N.,Wahba, H.M.,Stocker, T.,Akhrymuk, M.,Akhrymuk, I.,Panny, L.,Bracci, N.,Cafaro, R.,Sastre, D.,Silberfarb, A.,O'Maille, P.,Omichinski, J.,Kehn-Hall, K.
An LIR motif in the Rift Valley fever virus NSs protein is critical for the interaction with LC3 family members and inhibition of autophagy.
Plos Pathog., 20:e1012093-e1012093, 2024

PubMed Abstract: Rift Valley fever virus (RVFV) is a viral zoonosis that causes severe disease in ruminants and humans. The nonstructural small (NSs) protein is the primary virulence factor of RVFV that suppresses the host's antiviral innate immune response. Bioinformatic analysis and AlphaFold structural modeling identified four putative LC3-interacting regions (LIR) motifs (NSs 1-4) in the RVFV NSs protein, which suggest that NSs interacts with the host LC3-family proteins. Using, isothermal titration calorimetry, X-ray crystallography, co-immunoprecipitation, and co-localization experiments, the C-terminal LIR motif (NSs4) was confirmed to interact with all six human LC3 proteins. Phenylalanine at position 261 (F261) within NSs4 was found to be critical for the interaction of NSs with LC3, retention of LC3 in the nucleus, as well as the inhibition of autophagy in RVFV infected cells. These results provide mechanistic insights into the ability of RVFV to overcome antiviral autophagy through the interaction of NSs with LC3 proteins.

PubMed: 38512999
DOI: 10.1371/journal.ppat.1012093

実験手法

X-RAY DIFFRACTION (1.27 Å)