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Human FMRP contains an integral tandem Agenet (Tudor) and KH motif in the amino terminal domain.

ABSTRACT: Fragile X syndrome, a common cause of intellectual disability and autism, is due to mutational silencing of the FMR1 gene leading to the absence of its gene product, fragile X mental retardation protein (FMRP). FMRP is a selective RNA binding protein owing to two central K-homology domains and a C-terminal arginine-glycine-glycine (RGG) box. However, several properties of the FMRP amino terminus are unresolved. It has been documented for over a decade that the amino terminus has the ability to bind RNA despite having no recognizable functional motifs. Moreover, the amino terminus has recently been shown to bind chromatin and influence the DNA damage response as well as function in the presynaptic space, modulating action potential duration. We report here the amino terminal crystal structures of wild-type FMRP, and a mutant (R138Q) that disrupts the amino terminus function, containing an integral tandem Agenet and discover a novel KH motif.

SUBMITTER: Myrick LK

PROVIDER: S-EPMC4381759 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Human FMRP contains an integral tandem Agenet (Tudor) and KH motif in the amino terminal domain.

Myrick Leila K LK Hashimoto Hideharu H Cheng Xiaodong X Warren Stephen T ST

Human molecular genetics 20141120 6

Fragile X syndrome, a common cause of intellectual disability and autism, is due to mutational silencing of the FMR1 gene leading to the absence of its gene product, fragile X mental retardation protein (FMRP). FMRP is a selective RNA binding protein owing to two central K-homology domains and a C-terminal arginine-glycine-glycine (RGG) box. However, several properties of the FMRP amino terminus are unresolved. It has been documented for over a decade that the amino terminus has the ability to b ...[more]

PMID: 25416280

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