| 项目编号 |
PRJCA024613 |
| 项目标题 |
AARS1/2 senses L-lactate for cGAS regulation as lysine lactyltransferase |
| 涉及领域 |
Medical |
| 数据类型 |
Transcriptome or Gene expression
|
| 物种名称 |
Homo sapiens
Bacteria
|
| 描述信息 |
L-Lactate has been recently reported to modify proteins via lactylation but how this occurs is not clear. Here we identifishowed AARS1 and AARS2 (AARS1/2) as intracellular L-lactate sensor, required for L-lactate to stimulate lysine lactylome in cells. AARS1/2 and the evolutionarily conserved E. coli ortholog AlaRS bind to L-lactate with a dissociation constant of 7.5-20 micromolar affinity and they directly catalyze L-lactate for an ATP-dependent lactylation on lysine acceptor end. In response to L-lactate, AARS2 associates with cGAS and mediates its lactylation and inactivation in cells and mice. By establishing a genetic code expansion orthogonal system for lactyl-lysine incorporation, we demonstrated the presence of a lactyl moiety at specific cGAS N-terminal site abolishes cGAS LLPS and the DNA-sensing both in vitro and in vivo. Whereas the lactyl-mimetic knock-in inhibits cGAS, lactyl-resistant knock-in protects mice against the innate-immune evasion induced by high levels of L-lactate. |
| 样品范围 |
Multiisolate |
| 发布日期 |
2024-04-23 |
| 出版信息 |
| PubMed ID |
文章标题 |
杂志名称 |
Doi |
发表年份 |
| 39322678
|
AARS1 and AARS2 sense l-lactate to regulate cGAS as global lysine lactyltransferases
|
Nature
|
10.1038/s41586-024-07992-y
|
2024
|
| 41366033
|
Stepped collisional energy improves protein acylation identification by eliminating positional bias of cyclic immonium ions
|
Communications Chemistry
|
10.1038/s42004-025-01826-2
|
2025
|
|
|
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| Ministry of Science and Technology of the People's Republic of China (MOST)
|
|
2021YFA1101000
|
|
| National Natural Science Foundation of China (NSFC)
|
|
U20A20393
|
|
| National Natural Science Foundation of China (NSFC)
|
|
U20A201376
|
|
|
|
| 提交者 |
Zhang
Long (l_zhang@zju.edu.cn)
|
| 提交单位 |
Life Sciences Institute, Zhejiang University |
| 提交日期 |
2024-03-23 |
