A metazoan ortholog of SpoT hydrolyzes ppGpp and functions in starvation responses

被引：97

作者：

Sun, Dawei ^{[1
,2
]}

Lee, Gina ^{[3
,4
,5
]}

Lee, Jun Hee ^{[3
]}

Kim, Hye-Yeon ^{[1
]}

Rhee, Hyun-Woo ^{[6
]}

Park, Seung-Yeol ^{[3
]}

Kim, Kyung-Jin ^{[7
]}

Kim, Yongsung ^{[3
,4
,5
]}

Kim, Bo Yeon ^{[8
]}

Hong, Jong-In ^{[6
]}

Park, Chankyu ^{[3
]}

Choy, Hyon E. ^{[9
]}

Kim, Jung Hoe ^{[3
]}

Jeon, Young Ho ^{[1
,2
]}

Chung, Jongkyeong ^{[3
,4
,5
,10
]}

机构：

[1] Korea Basic Sci Inst, Div Magnet Resonance, Chungbuk, South Korea

[2] Univ Sci & Technol, Dept Bioanalyt Sci, Taejon, South Korea

[3] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea

[4] Seoul Natl Univ, Natl Creat Res Initiat Ctr, Seoul, South Korea

[5] Seoul Natl Univ, Sch Biol Sci, Seoul, South Korea

[6] Seoul Natl Univ, Dept Chem, Seoul, South Korea

[7] Pohang Univ Sci & Technol, Pohang Accelerator Lab, Pohang, South Korea

[8] Korea Res Inst Biosci & Biotechnol, Chungbuk, South Korea

[9] Chonnam Natl Univ, Coll Med, Dept Microbiol, Kwangju, South Korea

[10] Seoul Natl Univ, Inst Mol Biol & Genet, Seoul, South Korea

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2010年 / 17卷 / 10期

关键词：

STRINGENT RESPONSE; GUANOSINE TETRAPHOSPHATE; PROTEIN-SYNTHESIS; BACTERIAL; (P)PPGPP; RELA; GENE; ACID; TRANSCRIPTION; CHLOROPLASTS;

D O I：

10.1038/nsmb.1906

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In nutrient-starved bacteria, RelA and SpoT proteins have key roles in reducing cell growth and overcoming stresses. Here we identify functional SpoT orthologs in metazoa ( named Mesh1, encoded by HDDC3 in human and Q9VAM9 in Drosophila melanogaster) and reveal their structures and functions. Like the bacterial enzyme, Mesh1 proteins contain an active site for ppGpp hydrolysis and a conserved His-Asp-box motif for Mn2+ binding. Consistent with these structural data, Mesh1 efficiently catalyzes hydrolysis of guanosine 3',5'-diphosphate ( ppGpp) both in vitro and in vivo. Mesh1 also suppresses SpoT-deficient lethality and RelA-induced delayed cell growth in bacteria. Notably, deletion of Mesh1 ( Q9VAM9) in Drosophila induces retarded body growth and impaired starvation resistance. Microarray analyses reveal that the amino acid-starved Mesh1 null mutant has highly downregulated DNA and protein synthesis-related genes and upregulated stress-responsible genes. These data suggest that metazoan SpoT orthologs have an evolutionarily conserved function in starvation responses.

引用

页码：1188 / +

页数：8

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