HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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

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 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.
AuthorsG Musco, G Stier, C Joseph, M A Castiglione Morelli, M Nilges, T J Gibson, A Pastore
JournalCell (Cell) Vol. 85 Issue 2 Pg. 237-45 (Apr 19 1996) ISSN: 0092-8674 [Print] United States
PMID8612276 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Carrier Proteins
  • Proteins
  • RNA-Binding Proteins
  • Isoleucine
  • high density lipoprotein binding protein
  • Asparagine
Topics
  • Asparagine (genetics)
  • Binding Sites (physiology)
  • Carrier Proteins
  • Fragile X Syndrome (genetics, 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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: