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

Cell. 1996 Apr 19;85(2):237-45. doi: 10.1016/s0092-8674(00)81100-9.


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 beta alpha alpha beta beta alpha 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asparagine / genetics
  • Binding Sites / physiology
  • Carrier Proteins*
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / metabolism*
  • Humans
  • Isoleucine / genetics
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Mutagenesis / physiology
  • Mutagenesis, Site-Directed
  • Phenotype
  • Protein Conformation
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • RNA-Binding Proteins / chemistry*
  • Sequence Homology, Amino Acid


  • Carrier Proteins
  • Proteins
  • RNA-Binding Proteins
  • Isoleucine
  • high density lipoprotein binding protein
  • Asparagine

Associated data

  • GENBANK/D26120
  • GENBANK/J02638
  • GENBANK/J03453
  • GENBANK/L25598
  • GENBANK/M31304
  • GENBANK/M64098
  • GENBANK/M88108
  • GENBANK/M91593
  • GENBANK/S65791
  • GENBANK/S74678
  • GENBANK/S75665
  • GENBANK/U04840
  • GENBANK/U05040
  • GENBANK/U10438
  • GENBANK/U15928
  • GENBANK/U19858
  • GENBANK/U23177
  • GENBANK/U25165
  • GENBANK/U31501
  • GENBANK/X75947
  • GENBANK/X77291
  • GENBANK/Z36101