6DKU

Crystal structure of Myotis VP35 mutant of interferon inhibitory domain

Summary for 6DKU

• Entry DOI: 10.2210/pdb6dku/pdb
• Descriptor: VP35 (2 entities in total)
• Functional Keywords: unknown function
• Biological source: Myotis lucifugus (Little brown bat); More
• Total number of polymer chains: 1
• Total formula weight: 14505.61

Authors

Liu, H.,Ginell, G.M.,Keefe, L.J.,Leung, D.W.,Amarasinghe, G.K. (deposition date: 2018-05-30, release date: 2018-07-18, Last modification date: 2023-10-11)

Primary citation

Edwards, M.R.,Liu, H.,Shabman, R.S.,Ginell, G.M.,Luthra, P.,Ramanan, P.,Keefe, L.J.,Kollner, B.,Amarasinghe, G.K.,Taylor, D.J.,Leung, D.W.,Basler, C.F.
Conservation of Structure and Immune Antagonist Functions of Filoviral VP35 Homologs Present in Microbat Genomes.
Cell Rep, 24:861-872.e6, 2018

PubMed Abstract: Non-retroviral integrated RNA viral sequences (NIRVs) potentially encoding ∼280 amino acid homologs to filovirus VP35 proteins are present across the Myotis genus of bats. These are estimated to have been maintained for ∼18 million years, indicating their co-option. To address the reasons for co-option, 16 Myotis VP35s were characterized in comparison to VP35s from the extant filoviruses Ebola virus and Marburg virus, in which VP35s play critical roles in immune evasion and RNA synthesis. The Myotis VP35s demonstrated a conserved suppression of innate immune signaling, albeit with reduced potency, in either human or Myotis cells. Their attenuation reflects a lack of dsRNA binding that in the filoviral VP35s correlates with potent suppression of interferon responses. Despite divergent function, evolution has preserved in Myotis the structure of the filoviral VP35s, indicating that this structure is critical for co-opted function, possibly as a regulator of innate immune signaling.

PubMed: 30044983
DOI: 10.1016/j.celrep.2018.06.045

Experimental method

X-RAY DIFFRACTION (2.6 Å)