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 journalArticle

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

Fingerprint

Fragile X Syndrome
RNA
Intellectual Disability
Substitution reactions
Association reactions
Phenotype
Mutation
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Musco, G., Stier, G., Joseph, C., Morelli, M. A. C., Nilges, M., Gibson, T. J., & Pastore, A. (1996). Three-dimensional structure and stability of the KH domain: Molecular insights into the fragile X syndrome. Cell, 85(2), 237-245. https://doi.org/10.1016/S0092-8674(00)81100-9

Three-dimensional structure and stability of the KH domain : Molecular insights into the fragile X syndrome. / Musco, Giovanna; Stier, Gunter; Joseph, Catherine; Morelli, M. A C; Nilges, Michael; Gibson, Toby J.; Pastore, Annalisa.

In: Cell, Vol. 85, No. 2, 19.04.1996, p. 237-245.

Research output: Contribution to journalArticle

Musco, G, Stier, G, Joseph, C, Morelli, MAC, Nilges, M, Gibson, TJ & Pastore, A 1996, 'Three-dimensional structure and stability of the KH domain: Molecular insights into the fragile X syndrome', Cell, vol. 85, no. 2, pp. 237-245. https://doi.org/10.1016/S0092-8674(00)81100-9
Musco, Giovanna ; Stier, Gunter ; Joseph, Catherine ; Morelli, M. A C ; Nilges, Michael ; Gibson, Toby J. ; Pastore, Annalisa. / Three-dimensional structure and stability of the KH domain : Molecular insights into the fragile X syndrome. In: Cell. 1996 ; Vol. 85, No. 2. pp. 237-245.
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