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PDBsum entry 5jc3
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Immune system
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PDB id
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5jc3
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References listed in PDB file
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Key reference
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Title
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Structural analysis of dsrna binding to anti-Viral pattern recognition receptors lgp2 and mda5.
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Authors
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E.Uchikawa,
M.Lethier,
H.Malet,
J.Brunel,
D.Gerlier,
S.Cusack.
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Ref.
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Mol Cell, 2016,
62,
586-602.
[DOI no: ]
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PubMed id
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Abstract
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RIG-I and MDA5 sense virus-derived short 5'ppp blunt-ended or long dsRNA,
respectively, causing interferon production. Non-signaling LGP2 appears to
positively and negatively regulate MDA5 and RIG-I signaling, respectively.
Co-crystal structures of chicken (ch) LGP2 with dsRNA display a fully or
semi-closed conformation depending on the presence or absence of nucleotide.
LGP2 caps blunt, 3' or 5' overhang dsRNA ends with 1 bp longer overall
footprint than RIG-I. Structures of 1:1 and 2:1 complexes of chMDA5 with short
dsRNA reveal head-to-head packing rather than the polar head-to-tail orientation
described for long filaments. chLGP2 and chMDA5 make filaments with a similar
axial repeat, although less co-operatively for chLGP2. Overall, LGP2 resembles a
chimera combining a MDA5-like helicase domain and RIG-I like CTD supporting
both stem and end binding. Functionally, RNA binding is required for
LGP2-mediated enhancement of MDA5 activation. We propose that LGP2 end-binding
may promote nucleation of MDA5 oligomerization on dsRNA.
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