2015 Fiscal Year Final Research Report
Structural studies of nucleic acid sensing Toll-like receptors
| Project/Area Number |
25291010
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Partial Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Structural biochemistry
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2013-04-01 – 2016-03-31
|
| Keywords | Toll様受容体 / 自然免疫 / X線結晶解析 / 一本鎖核酸 |
|---|
| Outline of Final Research Achievements |
Innate immunity serves as the first line of defense against invading pathogens such as bacteria and viruses. Toll-like receptors (TLRs) are examples of innate immune receptors, which sense specific molecular patterns from pathogens and activate immune responses.
TLR8 recognizes single stranded (ss) RNA derived from bacterial and viral DNA. We solved the crystal structure of TLR8 in complex with ssRNA and revealed that TLR8 is a uridine senso. TLR8 can be synergistically activated by uridine and oligonucleotide degraded from ssRNATLR9 recognizes bacterial and viral DNA containing the Cytosine-phosphate-Guanine (CpG) dideoxynucleotide motif. Here we show the crystal structure of TLR9 bound to agonistic CpG-DNA, forming a symmetric TLR9/CpG-DNA complex with 2:2 stoichiometry. CpG-DNA was recognized by both protomers in the dimer, in particular by the N-terminal fragment (LRRNT-LRR10) from one protomer and the C-terminal fragment (LRR20-LRR22) from the other.
|
| Free Research Field |
構造生物学
|
