Three-dimensional structure and stability of the KH domain: Molecular insights into the fragile X syndrome

Giovanna Musco, Gunter Stier, Catherine Joseph, M. A C Morelli, Michael Nilges, Toby J. Gibson, Annalisa Pastore

Research output: Contribution to journalArticlepeer-review

Abstract

The KH module is a sequence motif found in a number of proteins that are known to be in close association with RNA. Experimental evidence suggests a direct involvement of KH in RNA binding. The human FMR1 protein, which has two KH domains, is associated with fragile X syndrome, the most common inherited cause of mental retardation. Here we present the three-dimensional solution structure of the KH module. The domain consists of a stable βααββα fold. On the basis of our results, we suggest a potential surface for RNA binding centered on the loop between the first two helices. Substitution of a well-conserved hydrophobic residue located on the second helix destroys the KH fold; a mutation of this position in FMR1 leads to an aggravated fragile X phenotype.

Original languageEnglish
Pages (from-to)237-245
Number of pages9
JournalCell
Volume85
Issue number2
DOIs
Publication statusPublished - Apr 19 1996

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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