Structural Analysis of dsRNA Binding to Anti-viral Pattern Recognition Receptors LGP2 and MDA5.
Mol Cell
; 62(4): 586-602, 2016 05 19.
Article
in En
| MEDLINE
| ID: mdl-27203181
ABSTRACT
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 11 and 21 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.
Full text:
1
Database:
MEDLINE
Main subject:
RNA, Double-Stranded
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RNA-Binding Proteins
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Adenosine Triphosphatases
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Avian Proteins
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Receptors, Pattern Recognition
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DEAD Box Protein 58
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Interferon-Induced Helicase, IFIH1
Limits:
Animals
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Humans
Language:
En
Year:
2016
Type:
Article