Summary information and primary citation
- PDB-id
-
5zsb;
DSSR-derived features in text and
JSON formats
- Class
- immune system
- Method
- X-ray (2.7 Å)
- Summary
- Crystal structure of monkey tlr7 in complex with imdq
and aauuaa
- Reference
-
Zhang Z, Ohto U, Shibata T, Taoka M, Yamauchi Y, Sato R,
Shukla NM, David SA, Isobe T, Miyake K, Shimizu T (2018):
"Structural
Analyses of Toll-like Receptor 7 Reveal Detailed RNA
Sequence Specificity and Recognition Mechanism of
Agonistic Ligands." Cell Rep,
25, 3371-3381.e5. doi: 10.1016/j.celrep.2018.11.081.
- Abstract
- Toll-like receptor 7 (TLR7) is an innate immune
receptor for single-stranded RNA (ssRNA) and has important
roles in infectious diseases. We previously reported that
TLR7 shows synergistic activation in response to two
ligands, guanosine and ssRNA. However, the specific ssRNA
sequence preference, detailed recognition mode of TLR7 and
its ligand, and molecular determinants of TLR7 and TLR8
selectivity remain unknown. Here, we report on TLR7 from a
large-scale crystallographic study combined with a
multifaceted approach. We reveal that successive
uridine-containing ssRNAs fully or moderately bind TLR7,
whereas single uridine-containing ssRNAs have reduced
affinities. We also reveal the detailed relationships
between the chemical structures of ligands and their
binding to TLR7. We demonstrate that an engineered TLR8
mutant alters its responsiveness to TLR7-specific ligands.
Finally, we identify guanosine 2',3'-cyclic phosphate
(2',3'-cGMP) as a possible endogenous ligand for TLR7 with
greater affinity than guanosine. The abundant structural
information will facilitate future development of
treatments targeting TLR7.
