8T2N

Crystal structure of GABARAP in complex with the LIR of NSs3

Summary for 8T2N

• Entry DOI: 10.2210/pdb8t2n/pdb
• Descriptor: Gamma-aminobutyric acid receptor-associated protein, Non-structural protein S (3 entities in total)
• Functional Keywords: rift valley fever virus, autophagy, lc3, gabarap, lir, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 33564.21

Authors

Ali, M.G.H.,Wahba, H.M.,Cyr, N.,Omichinski, J.G. (deposition date: 2023-06-06, release date: 2024-04-03)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.88 Å)