A tandem of SH3-like domains participates in RNA binding in KIN17, a human protein activated in response to genotoxics.
The human KIN17 protein is an essential nuclear protein conserved from yeast to human and expressed ubiquitously in mammals. Suppression of Rts2, the yeast equivalent of gene KIN17, renders the cells unviable, and silencing the human KIN17 gene slows cell growth dramatically. Moreover, the human gene KIN17 is up-regulated following exposure to ionizing radiations and UV light, depending on the integrity of the human global genome repair machinery. Its ectopic over-expression blocks S-phase progression by inhibiting DNA synthesis. The C-terminal region of human KIN17 is crucial for this anti-proliferation effect. Its high-resolution structure, presented here, reveals a tandem of SH3-like subdomains. This domain binds to ribonucleotide homopolymers with the same preferences as the whole protein. Analysis of its structure complexed with tungstate shows structural variability within the domain. The interaction with tungstate is mediated by several lysine residues located within a positively charged groove at the interface between the two subdomains. This groove could be the site of interaction with RNA, since mutagenesis of two of these highly conserved lysine residue weakens RNA binding.
le Maire
Albane
A
CEA, DSV, DIEP, Gif-sur-Yvette, F-91191, France.
Schiltz
Marc
M
Stura
Enrico A
EA
Pinon-Lataillade
Ghislaine
G
Couprie
Joël
J
Moutiez
Mireille
M
Gondry
Muriel
M
Angulo
Jaime F
JF
Zinn-Justin
Sophie
S
D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008239:Lysine; D009153:Mutagens / Q000494:pharmacology; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D017973:Tungsten Compounds / Q000737:chemistry; D018909:src Homology Domains
D004268:DNA-Binding Proteins; C489487:KIN protein, human; D009153:Mutagens; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D017973:Tungsten Compounds; D012313:RNA; D008239:Lysine; C045951:tungstate