6k1z
From Proteopedia
Crystal structure of farnesylated hGBP1
Structural highlights
Function[GBP1_HUMAN] Hydrolyzes GTP to GMP in two consecutive cleavage reactions. Exhibits antiviral activity against influenza virus. Promote oxidative killing and deliver antimicrobial peptides to autophagolysosomes, providing broad host protection against different pathogen classes.[1] Publication Abstract from PubMedThe guanylate-binding proteins (GBPs) belong to the dynamin superfamily of GTPases and function in cell-autonomous defense against intracellular pathogens. IpaH9.8, an E3 ligase from the pathogenic bacterium Shigella flexneri, ubiquitinates a subset of GBPs and leads to their proteasomal degradation. Here we report the structure of a C-terminally truncated GBP1 in complex with the IpaH9.8 Leucine-rich repeat (LRR) domain. IpaH9.8LRR engages the GTPase domain of GBP1, and differences in the Switch II and alpha3 helix regions render some GBPs such as GBP3 and GBP7 resistant to IpaH9.8. Comparisons with other IpaH structures uncover interaction hot spots in their LRR domains. The C-terminal region of GBP1 undergoes a large rotation compared to previously determined structures. We further show that the C-terminal farnesylation modification also plays a role in regulating GBP1 conformation. Our results suggest a general mechanism by which the IpaH proteins target their cellular substrates and shed light on the structural dynamics of the GBPs. Structural mechanism for guanylate-binding proteins (GBPs) targeting by the Shigella E3 ligase IpaH9.8.,Ji C, Du S, Li P, Zhu Q, Yang X, Long C, Yu J, Shao F, Xiao J PLoS Pathog. 2019 Jun 19;15(6):e1007876. doi: 10.1371/journal.ppat.1007876., eCollection 2019 Jun. PMID:31216343[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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