Crystal structure of the FTO protein reveals basis for its substrate specificity View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2010-04

AUTHORS

Zhifu Han, Tianhui Niu, Junbiao Chang, Xiaoguang Lei, Mingyan Zhao, Qiang Wang, Wei Cheng, Jinjing Wang, Yi Feng, Jijie Chai

ABSTRACT

Recent studies have unequivocally associated the fat mass and obesity-associated (FTO) gene with the risk of obesity. In vitro FTO protein is an AlkB-like DNA/RNA demethylase with a strong preference for 3-methylthymidine (3-meT) in single-stranded DNA or 3-methyluracil (3-meU) in single-stranded RNA. Here we report the crystal structure of FTO in complex with the mononucleotide 3-meT. FTO comprises an amino-terminal AlkB-like domain and a carboxy-terminal domain with a novel fold. Biochemical assays show that these two domains interact with each other, which is required for FTO catalytic activity. In contrast with the structures of other AlkB members, FTO possesses an extra loop covering one side of the conserved jelly-roll motif. Structural comparison shows that this loop selectively competes with the unmethylated strand of the DNA duplex for binding to FTO, suggesting that it has an important role in FTO selection against double-stranded nucleic acids. The ability of FTO to distinguish 3-meT or 3-meU from other nucleotides is conferred by its hydrogen-bonding interaction with the two carbonyl oxygen atoms in 3-meT or 3-meU. Taken together, these results provide a structural basis for understanding FTO substrate-specificity, and serve as a foundation for the rational design of FTO inhibitors. More... »

PAGES

1205

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature08921

DOI

http://dx.doi.org/10.1038/nature08921

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1052728573

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20376003


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nature08921'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nature08921'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nature08921'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nature08921'


 

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